Background/Objectives: The nephrotoxicity of immune checkpoint inhibitors (ICIs) combined with proton pump inhibitors (PPIs) has been recognized but lacks a comprehensive analysis. We conducted an in-depth investigation of renal adverse events (rAEs) associated with ICIs and different acid-suppressing agents (ASAs)-including PPIs, histamine-2 receptor antagonists (H2RAs), and potassium-competitive acid blockers (P-CABs)-using real-world data from the FDA's Adverse Event Reporting System (FAERS). Methods: We analyzed rAE reports from the FAERS database covering Q1 2004 to Q1 2023. Disproportionality analysis was conducted to identify rAEs associated with ICI or ASA monotherapy or combination therapy. Univariate logistic regression was employed to explore influencing factors. Results: No eligible rAE reports were retrieved for H2RAs and P-CABs. However, 6,775 reports in the ICI group, 54,055 reports in the PPI group, and 210 reports in the ICI-PPI combination therapy group were included in the final analysis. In PPI-ICI combination settings, tubulointerstitial nephritis had the highest reporting frequency and signal intensity; the overall risk of rAEs was significantly elevated compared to ICI or PPI monotherapy, with reporting odds ratios of 14. 65 (95% confidence interval [CI] 12.93-16.58) and 3.24 (95% CI 2.87-3.66), respectively; the median onset time was shortest at 21 days (interquartile range 5.5-135); and PD-1 monotherapy, omeprazole, and rabeprazole were associated with higher rAE risks. Conclusions: Our findings confirm that the combination of PPIs (but not other ASAs) with ICIs further increases the risk of various acute and chronic rAEs. Healthcare providers should exercise caution when managing patients on these therapies.

Tubulointerstitial nephritis (TIN) is an important disease involving a diverse set of factors that can cause both acute kidney injury and chronic kidney disease. The purpose of this cross-sectional study was to clarify the causative diseases and clinicopathological characteristics of TIN using the Japan Renal Biopsy Registry (J-RBR).

This cross-sectional study analyzed data from 22,049 cases registered in the J-RBR between 2018 and 2022. Clinicopathological findings at diagnosis were investigated.

Of the enrolled cases, 913 were diagnosed with TIN. "Drug-induced" was the most common (232 cases, 25.7%), followed by "IgG4-related kidney disease" (124 cases, 13.7%). Of "Drug-induced" TIN cases, "Chemotherapy-related" was the most common cause (63 cases, 27.2%), including 47 cases of "immune checkpoint inhibitor (ICI)-associated" TIN. IgM-positive plasma cell-rich TIN (IgMPC-TIN), which has been the focus of much attention in recent years, was also included, with 9 cases.

This is the first report of the clinicopathological findings of TIN patients in a large-scale, nationwide registry of renal biopsies. It was possible to identify recent trends in causative diseases, including an increase in chemotherapy-related TIN and IgMPC-TIN.

Cancer immunotherapy, encompassing both experimental and standard-of-care therapies, has emerged as a promising approach to harnessing the immune system for tumor suppression. Experimental strategies, including novel immunotherapies and preclinical models, are actively being explored, while established treatments, such as immune checkpoint inhibitors (ICIs), are widely implemented in clinical settings. This comprehensive review examines the historical evolution, underlying mechanisms, and diverse strategies of cancer immunotherapy, highlighting both its clinical applications and ongoing preclinical advancements. The review delves into the essential components of anticancer immunity, including dendritic cell activation, T cell priming, and immune surveillance, while addressing the challenges posed by immune evasion mechanisms. Key immunotherapeutic strategies, such as cancer vaccines, oncolytic viruses, adoptive cell transfer, and ICIs, are discussed in detail. Additionally, the role of nanotechnology, cytokines, chemokines, and adjuvants in enhancing the precision and efficacy of immunotherapies were explored. Combination therapies, particularly those integrating immunotherapy with radiotherapy or chemotherapy, exhibit synergistic potential but necessitate careful management to reduce side effects. Emerging factors influencing immunotherapy outcomes, including tumor heterogeneity, gut microbiota composition, and genomic and epigenetic modifications, are also examined. Furthermore, the molecular mechanisms underlying immune evasion and therapeutic resistance are analyzed, with a focus on the contributions of noncoding RNAs and epigenetic alterations, along with innovative intervention strategies. This review emphasizes recent preclinical and clinical advancements, with particular attention to biomarker-driven approaches aimed at optimizing patient prognosis. Challenges such as immunotherapy-related toxicity, limited efficacy in solid tumors, and production constraints are highlighted as critical areas for future research. Advancements in personalized therapies and novel delivery systems are proposed as avenues to enhance treatment effectiveness and accessibility. By incorporating insights from multiple disciplines, this review aims to deepen the understanding and application of cancer immunotherapy, ultimately fostering more effective and widely accessible therapeutic solutions.

While immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, they can elicit organ-related immune-related adverse events (irAEs) such as kidney injury. Here, our study evaluated the ability of a humanized immune system (HIS) tumor-bearing mouse model to investigate ICI-mediated kidney injury. Non-humanized (BRGS) and humanized (HIS-BRGS) mice were implanted with human breast cancer cells and treated with either nivolumab (anti-PD-1) or a combination of nivolumab and ipilimumab (anti-CTLA-4) for four weeks. Histopathological analysis revealed that HIS-BRGS mice treated with ICIs exhibited significant interstitial nephritis and vasculitis/periarteritis, consistent with kidney phenotypes observed in patients. Combination therapy resulted in more extensive kidney pathology than nivolumab alone and exhibited an accumulation of T helper cells in the affected areas. Importantly, our results suggest that HIS-BRGS mice can effectively recapitulate features of ICI-induced kidney injury observed in patients and can be used to study mechanisms and prevention strategies to limit irAEs.

Lung cancer (LC) is a leading cause of cancer-related mortality worldwide. The combination of immune checkpoint inhibitors (ICIs) with chemotherapy significantly extends survival but increases the risk of treatment-related toxicity. To explore the impact of adding pembrolizumab to pemetrexed and platinum on treatment-related toxicity, this study utilized the FDA Adverse Event Reporting System (FAERS) to assess the safety of pemetrexed and platinum with or without pembrolizumab in LC patients.

We collected data from FAERS database between the second quarter of 2017 and the third quarter of 2024. Disproportionality analysis was conducted using the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS). Additionally, comparative analysis was performed using the ROR method.

Among LC patients receiving chemotherapy alone (pemetrexed + platinum) and combination therapy (pembrolizumab + pemetrexed + platinum), adverse event (AE) reports were 2871 and 5443 cases, respectively. Compared to chemotherapy alone, combination therapy was associated with a higher risk of renal and urinary disorders, hepatobiliary disorders, and interstitial lung disease (ILD), pneumonitis and other AEs. Subgroup analysis revealed that gender and age may be influential factors in the occurrence of AEs. Combination therapy prolonged the time to onset of AEs.

In the real world, combination therapy increases the risk of certain AEs, particularly in specific patient subgroups. These findings emphasize the importance of personalized treatment strategies and AE monitoring, particularly during the first three months of therapy.

With the increasing popularity of immune checkpoint inhibitors (ICIs) in tumor treatment, the incidence of immune-related adverse events (irAEs), including acute kidney injury (AKI), is on the rise. Renal biopsy serves as the gold standard for determining the true etiology of AKI following ICIs administration; however, due to potential risks and associated losses with this procedure, comprehensive analysis of physiological data and predictive models are gradually being incorporated into clinical practice to differentiate AKI etiologies. These include criteria such as a ≥ 100% increase in serum creatinine (Scr) from baseline or a 50% increase accompanied by other pathological manifestations, renal replacement therapy (RRT), or absence of any other reasonable cause. Currently, cessation of ICIs and steroid therapy represent commonly employed treatment approaches; nevertheless, these strategies have inherent side effects and may not be feasible for certain patient populations, such as those with diabetes, posing challenges for clinicians. Recent studies have demonstrated that rituximab, mycophenolate mofetil (MMF), and infliximab can potentially replace steroid therapy in managing ICIs-induced AKI (ICIs-AKI), offering a novel therapeutic perspective. This review provides an overview of non-invasive methods for distinguishing between AKI following ICIs use and ICIs-AKI while discussing strategies for treating ICIs-AKI.

BACKGROUND Malignant peritoneal mesothelioma (MPM) is a rare and aggressive neoplasm, with low-grade epithelioid subtypes presenting diagnostic and therapeutic challenges. With nonspecific symptoms and diagnostic challenges, definitive diagnosis relies on histopathological and immunohistochemical analysis. This study reviews the current research on the epidemiology, diagnosis, and treatment of MPM, focusing on preserving fertility and achieving successful childbirth following surgery, chemotherapy, and immunotherapy, despite immune-related adverse events. CASE REPORT We report the case of a 44-year-old nulliparous woman, initially diagnosed with a uterine leiomyoma, who was incidentally found to have MPM during surgery. Diagnostic laparoscopy and subsequent imaging revealed extensive peritoneal involvement, confirmed by histopathology and immunohistochemistry. The patient's desire to preserve fertility complicated the treatment approach, leading to chemotherapy followed by immunotherapy, with complete disease control. Without evidence of disease recurrence or metastasis, the patient proceeded with in vitro fertilization (IVF) and embryo transfer. During an emergency cesarean section at 30 weeks 2 days of gestation, performed due to preterm premature rupture of membranes, intraabdominal residual tumors were discovered and excised. No evidence of malignancy was found elsewhere. CONCLUSIONS MPM is a rare disease, often with a delayed diagnosed due to nonspecific symptoms. Treatments like cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) improve survival for operable cases, while systemic therapies and immune-checkpoint inhibitors (ICIs) are options for inoperable cases; however, further research on early-detection biomarkers and the impact of ICIs on fertility is needed to enhance clinical practice. This case highlights the intricate balance between oncologic control and fertility preservation in MPM, illustrating the need for individualized treatment strategies.

Background/Objectives: Immune checkpoint inhibitors (ICIs) have generated a revolutionary approach in the treatment of cancer, but their effectiveness has been compromised by immune-related adverse events, including renal damage. Although rare, these effects are relevant because they have been related to poor patient prognoses. The objective of this review was to estimate the current incidence of nephrotoxicity in patients treated with single and double ICI therapies. Methods: A total of 1283 potential articles were identified, which were reduced to 50 after applying the exclusion and inclusion criteria. Results: This study reveals the increase in acute kidney injury associated with these drugs in the last decade and shows that, interestingly, combined therapies with ICIs does not lead to an increase in kidney damage compared with anti-CTLA-4. It also suggests that kidney damage could be underdiagnosed when it comes to interstitial nephritis, because definitive evidence requires a renal biopsy. Conclusions: In perspective, these conclusions could guide clinicians in making decisions for therapy personalization and highlight the need to search for new diagnostic systems that are more sensitive and specific to the type of damage and could replace the biopsy.

Immune checkpoint inhibitor (ICI) therapy is a cornerstone treatment for many cancers, but it can induce severe immunotoxicity, including acute interstitial nephritis (AIN). Currently, kidney biopsy is required to differentiate ICI-AIN from other causes of acute kidney injury (AKI). However, this invasive approach can lead to morbidity, delayed glucocorticoid treatment for patients with AIN, and unnecessarily prolonged suspension of ICI therapy in non-AIN patients. Delayed or incorrect diagnosis of ICI-AIN is particularly detrimental, as over 50% of patients are at risk of permanent renal damage. Thus, there is an urgent need for non-invasive biomarkers that can rapidly and accurately distinguish ICI-AIN from other causes of AKI.The urine and plasma proteome contain actively secreted proteins that provide real-time insights into dynamic physiological processes. However, identification of effective biomarkers of disease using established technologies such as proximity ligation assays (PLA) and bead-based immunoassays is challenging due to their limited sensitivity and loss of precision in multiplex analysis.To address this, we employed cutting-edge NUcleic acid Linked Immuno-Sandwich Assay (NULISA) technology to measure protein expression in urine and plasma samples from AKI patients undergoing ICI therapy. NULISA offers 10,000-fold greater precision than PLA, enabling quantification of over 200 inflammatory proteins with unprecedented precision. Our analysis revealed that urine was more sensitive and specific than plasma in distinguishing ICI-AIN from non-AIN cases. Pathway analyses highlighted the involvement of JAK-STAT and tumor necrosis factor (TNF) signaling in ICI-AIN pathogenesis. We identified several novel urine biomarkers, including IL-5, Fas, TNFSF4, CD274, IL-20, TNFSF15, TSLP, TREM1 and CCL1 while confirming previously reported markers such as CXCL9 and TNF-α. Using statistical and machine learning methods, we constructed a novel urine biomarker signature-IL-5+Fas-that achieved an area under the curve of 0.94 for diagnosing ICI-AIN.By leveraging high-sensitivity proteomics, we developed a non-invasive strategy for diagnosing ICI-AIN. This approach will enable earlier intervention to mitigate immunotoxicity, preservation of antitumor efficacy of ICI therapy in non-AIN patients, and safe rechallenge of ICI therapy in patients previously treated for ICI-AIN.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer and are now the backbone of therapy for several malignancies. However, ICIs can cause a spectrum of kidney immune-related adverse events including acute kidney injury (AKI), most commonly manifesting as acute interstitial nephritis (AIN), although glomerular disease and electrolyte disturbances have also been reported. In this position statement by the American Society of Onco-nephrology (ASON), we summarize the incidence and risk factors for ICI-AKI, pathophysiological mechanisms, and clinicopathologic features of ICI-AKI. We also discuss novel diagnostic approaches and promising biomarkers for ICI-AKI. From expert panel consensus, we provide clinical practice points for the initial assessment and diagnosis of ICI-AKI, management and immunosuppressive therapy, and consideration for rechallenge with ICI following AKI episodes. In addition, we explore ICI use in special populations, such as kidney transplant recipients, and propose key areas of focus for future research and clinical investigation.

Minimal change disease (MCD) is a common cause of nephrotic syndrome in children and adults. Immune dysregulation is a contributor, but the relative roles of individual components of the immune system in MCD pathogenesis remain unclear.

Here, we present 2 patients with defects in immune tolerance mechanisms that developed MCD associated with anti-nephrin antibodies. The first patient had a pathogenic deletion in FOXP3, leading to reduced regulatory T cells. Serum could not be obtained from this patient during the active phase of MCD to directly establish the presence of anti-nephrin antibodies. However, this patient demonstrated IgG dusting over podocyte cell bodies by immunofluorescence microscopy, as well as colocalization of IgG with nephrin in confocal microscopy. The second patient developed MCD in the context of immune checkpoint inhibitor treatment for metastatic carcinoma. Anti-nephrin antibodies were detected in this patient during active disease. The patient's kidney biopsy also showed evidence of binding of anti-nephrin antibodies within the glomeruli.

These cases demonstrate that genetic and iatrogenic mechanisms of breakdown in peripheral tolerance can lead to MCD.

Immune checkpoint inhibitor-associated acute kidney injury (ICI-AKI) is the most common renal complication and has attracted increasing amounts of attention. However, studies on this topic in Chinese cancer patients are very limited. Therefore, we conducted a retrospective study on the incidence, risk factors, clinical features and renal recovery of ICI-AKI in all patients with malignancies treated with ICIs in Shandong Provincial Hospital Affiliated to Shandong First Medical University.

In this single-center retrospective cohort study, the data of 904 patients who received immune checkpoint inhibitors (ICIs) treatment were retrospectively analyzed. Multivariable logistic regression was used to identify the predictors of ICI-AKI.

A total of 46 of 904 patients receiving ICIs developed ICI-AKI, and the incidence of ICI-AKI was 5.1%. Patients developed ICI-AKI at a median of 9 weeks (IQR 3-23) after ICIs initiation. A lower baseline estimated glomerular filtration rate (eGFR) and use of antibiotics were associated with a higher risk of ICI-AKI. Renal recovery occurred in 17 patients (46%) at a median of 4 weeks (IQR 2-8) after ICI-AKI, including 16 (43%) with complete recovery and 1 (3%) with partial recovery. Of the 14 rechallenged patients, only one developed recurrent ICI-AKI.

Patients with ICI-AKI were more likely to have impaired renal function at baseline and after treatment with antibiotics. Approximately half of the patients achieved renal recovery.

Chronic kidney disease (CKD) and cancer constitute two major public health burdens, and both are on the rise. Moreover, the number of patients affected simultaneously by both conditions is growing. The potential nephrotoxic effect of cancer therapies is particularly important for patients with CKD, as they are also affected by several comorbidities. Therefore, administering the right therapy at the right dose for patients with decreased kidney function can represent a daunting challenge. We review in detail the renal toxicities of anticancer therapies, i.e. conventional chemotherapy, targeted therapy, immune checkpoint inhibitors and radioligand therapies, issue recommendations for patient monitoring along with guidance on when to withdraw treatment and suggest dosage guidelines for select agents in advanced stage CKD. Various electrolytes disturbances can occur as the result of the administration of anticancer agents in the patient with decreased kidney function. These patients are prone to developing hyponatremia, hyperkalemia and other metabolic abnormalities because of a decreased glomerular filtration rate. Therefore, all electrolytes, minerals and acid base status should be checked at baseline and before each administration of chemotherapeutic agents. Moreover, studies on patients on kidney replacement therapy are very limited and only single cases or small case series have been published. Therefore, clinical therapeutical decisions in cancer patients with decreased function should be made by multidisciplinary teams constituted of medical oncologists, nephrologists and other specialists. Onconephrology is an evolving and expanding subspecialty. It is crucial to consider anticancer drug treatment in these patients and offer them a chance to be treated effectively.

Brentuximab vedotin is a combination monoclonal antibody to anti-CD30 conjugated to the anti-tubulin agent monomethyl auristatin E. It is approved for the treatment of mycosis fungoides, Hodgkin's lymphoma, and systemic anaplastic large cell lymphoma. Brentuximab has been associated with a number of potential adverse reactions; however, reports of renal complications are rare. A 73-year-old male with mycosis fungoides was admitted to hospital with acute kidney injury following his third cycle of brentuximab. The patient's serum creatinine (SCr) was 122 µmol/L with an estimated glomerular filtration rate (eGFR) of 58 mL/min/1.73 m2 at baseline. Following brentuximab, his SCr peaked at 1073 µmol/L over a 4-week period. Acute interstitial nephritis (AIN) was diagnosed after other causes of acute kidney injury were ruled out and subsequently confirmed on kidney biopsy. The patient was started on prednisone 50 mg daily. This was continued for 3 weeks, followed by a 5-week taper. The patient's SCr decreased to 156 µmol/L by completion of the prednisone taper. He was not rechallenged with brentuximab. A kidney biopsy confirmed AIN in keeping with injury from an immune checkpoint inhibitor (ICI). However, brentuximab is not an ICI. The AIN from ICIs typically has tubulointerstitial inflammatory infiltrate comprised of T lymphocytes such as the case presented here. Therefore, this represents both a novel histopathologic finding in AIN from a non-ICI medication and a rare complication of brentuximab, previously only presented in abstract form.

Over the last 13 years, the use of immune checkpoint inhibitor (ICI) therapy has grown remarkably, owing to their unprecedented anti-tumor efficacy in certain tumor groups. With increased use of ICIs, we are seeing immune-related adverse events (irAEs) more frequently. Renal irAEs, such as ICI-associated acute kidney injury (ICI-AKI), are reported in 2%-5% of patients treated with ICIs, with acute tubulointerstitial nephritis (ATIN) as the most common histopathologic lesion, though various forms of glomerulonephritis have also been reported. Modifiable risk factors for ICI-AKI include concurrent use of ATIN-associated drugs, like proton pump inhibitors, non-steroidal anti-inflammatory drugs and antibiotics, and dual ICI therapy with both Cytotoxic T-lymphocyte Associated Protein 4 (CTLA-4) and Programmed Cell Death Protein 1 and its ligand (PD1/PDL-1) blockade. Kidney biopsies remain the diagnostic modality of choice, though several promising non-invasive biomarkers, which have not yet been broadly clinically validated have emerged. The treatment of ICI-AKI involves holding ICIs, discontinuation of ATIN-associated drugs and initiation of immunosuppression with corticosteroids as first-line therapy. With prompt treatment initiation, most patients achieve full or partial renal recovery, allowing for re-challenge with ICI. However, a subset of patients will require additional steroid-sparing therapies for corticosteroid-dependent or refractory ICI-AKI. Here we review developments in our understanding of the pathophysiology of ICI-AKI, the approach to diagnosis (with a focus on the emergence of novel diagnostic tools), prognostic factors and the current evidence for establishing treatment standards for ICI-AKI. As the evidence base remains largely retrospective, we identify questions that would benefit from future prospective studies in the diagnosis, management and prognostication of ICI-AKI.

The increased use of immune checkpoint inhibitors (ICIs) across cancer programs has created the need for standardized monitoring and management of immune-related adverse events (irAEs). Delayed recognition without appropriate treatment can have serious and life-threatening consequences. The management of irAEs presents a unique set of challenges that must be addressed at a multidisciplinary level. Although various national and international guidelines and working groups provide high-level recommendations for the management of irAEs, practical guidance is lacking. Furthermore, timely collaboration between specialists requires institutional protocols that enable the early recognition, assessment, and treatment of irAEs. Such protocols should be developed by institution specialists and include algorithms for all healthcare providers involved in the care of patients treated with ICIs. At William Osler Health System in Brampton, Ontario, practical step-by-step multidisciplinary treatment approaches with recommendations for the management of irAEs were developed in collaboration with experts across Canada. Here, we provide an in-depth description of the approaches, outlining baseline investigations prior to the initiation of ICIs, as well as the monitoring and management of irAEs based on symptoms, severity, and involved organ systems. We encourage other centres to adapt and modify our approaches according to their specific needs and requirements.

Immune checkpoint inhibitor (ICI) therapy has enabled a paradigm shift in Oncology, with the treatment of metastatic cancer in certain tumor types becoming akin to the treatment of chronic disease. Kidney transplant recipients (KTR) are at increased risk of developing cancer compared to the general population. Historically, KTR were excluded from ICI clinical trials due to concern for allograft rejection and decreased anti-tumor efficacy. While early post-marketing data revealed an allograft rejection risk of 40%-50%, 2 recent small prospective trials have demonstrated lower rates of rejection of 0%-12%, suggesting that maintenance immunosuppression modification prior to ICI start modulates rejection risk. Moreover, objective response rates induced by ICI for the treatment of advanced or metastatic skin cancer, the most common malignancy in KTR, have been comparable to those achieved by immune intact patients. Non-invasive biomarkers may have a role in risk-stratifying patients before starting ICI, and monitoring for rejection, though allograft biopsy is required to confirm diagnosis. This clinically focused review summarizes current knowledge on complications of ICI use in KTR, including their mechanism, risk mitigation strategies, non-invasive biomarker use, approaches to treatment of rejection, and suggestions for future directions in research.

Immune checkpoint inhibitors are humanized antibodies that inhibit downregulatory receptors on T cells, enhancing the antitumor activity of these cells. However, they have been associated with a wide range of systemic immune-related adverse events, including renal toxicities, among others. Most renal immune-related adverse events are acute interstitial nephritis causing acute kidney injury. Recently, immune checkpoint inhibitors-associated glomerular diseases, including IgA nephropathy, have been reported in adults. Most of the adult cases with glomerular involvement had also concomitant acute interstitial nephritis and acute kidney injury. We present the first pediatric case of IgA nephropathy without acute kidney injury during nivolumab treatment.

A 74-year-old Japanese male with lung squamous cell carcinoma received his first dose of immune checkpoint inhibitors (ICIs): ipilimumab and nivolumab. He developed acute kidney injury (AKI) and was admitted to our department. We diagnosed kidney immune-related adverse effects (irAE), and a kidney biopsy revealed acute tubulointerstitial nephritis. We started oral prednisolone (PSL) and his AKI immediately improved. The patient maintained stable findings after PSL was tapered off. However, seven months after the ICI administration, he developed rapid progressive glomerular nephritis and was admitted to our department again. The second kidney biopsy showed findings consistent with anti-glomerular basement membrane glomerulonephritis. Although the patient was treated with pulse methylprednisolone followed by oral PSL and plasma exchange, he became dependent on maintenance hemodialysis. To our knowledge, no case report has described two different types of biopsy-proven nephritis. In cases of suspected relapsing kidney irAEs, both a relapse of previous nephritis and the development of another type of nephritis should be considered.

Although the patient survival rate for many malignancies has been improved with immune checkpoint inhibitors (ICIs), some patients experience various immune-related adverse events (irAEs). IrAEs impact several organ systems, including the kidney. With anti-programmed cell death protein 1 (PD-1) therapy (pembrolizumab), kidney-related adverse events occur relatively rarely compared with other irAEs. However, the occurrence of AKI usually leads to anti-PD-1 therapy interruption or discontinuation. Therefore, there is an urgent need to clarify the mechanisms of renal irAEs (R-irAEs) to facilitate early management. This study aimed to analyse the characteristics of peripheral blood mononuclear cells (PBMCs) in R-irAEs.

PBMCs were collected from three patients who developed R-irAEs after anti-PD-1 therapy and three patients who did not. The PBMCs were subjected to scRNA-seq to identify cell clusters and differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analyses were performed to investigate the most active biological processes in immune cells.

Fifteen cell clusters were identified across the two groups. FOS, RPS26, and JUN were the top three upregulated genes in CD4+ T cells. The DEGs in CD4+ T cells were enriched in Th17 differentiation, Th1 and Th2 cell differentiation, NF-kappa B, Nod-like receptor, TNF, IL-17, apoptosis, and NK cell-mediated cytotoxicity signaling pathways. RPS26, TRBV25-1, and JUN were the top three upregulated genes in CD8+ T cells. The DEGs in CD8+ T cells were enriched in Th17 cell differentiation, antigen processing and presentation, natural killer cell-mediated cytotoxicity, the intestinal immune network for IgA production, the T-cell receptor signalling pathway, Th1 and Th2 cell differentiation, the phagosome, and cell adhesion molecules.

In conclusion, R-irAEs are associated with immune cell dysfunction. DEGs and their enriched pathways identified in CD4+ T cells and CD8+ T cells play important roles in the development of renal irAEs related to anti-PD-1 therapy. These findings offer fresh perspectives on the pathogenesis of renal damage caused by anti-PD-1 therapy.

Renal injury, a prevalent clinical outcome with multifactorial etiology, imposes a substantial burden on society. Currently, there remains a lack of effective management and treatments. Extensive research has emphasized the diverse biological effects of natural polysaccharides, which exhibit promising potential for mitigating renal damage. This review commences with the pathogenesis of four common renal diseases and the shared mechanisms underlying renal injury. The renoprotective roles of polysaccharides in vivo and in vitro are summarized in the following five aspects: anti-oxidative stress effects, anti-apoptotic effects, anti-inflammatory effects, anti-fibrotic effects, and gut modulatory effects. Furthermore, we explore the structure-activity relationship and bioavailability of polysaccharides in relation to renal injury, as well as investigate their utility as biomaterials for alleviating renal injury. The clinical experiments of polysaccharides applied to patients with chronic kidney disease are also reviewed. Broadly, this review provides a comprehensive perspective on the research direction of natural polysaccharides in the context of renal injury, with the primary aim to serve as a reference for the clinical development of polysaccharides as pharmaceuticals and prebiotics for the treatment of kidney diseases.

Acute kidney injury (AKI) has been well described as a complication of immune checkpoint inhibitor therapy. We present a series of patients, the majority with lung adenocarcinoma, who developed AKI while actively receiving immune checkpoint inhibitors.

This is a retrospectively analyzed clinical case series of six patients treated at City of Hope Comprehensive Cancer Center. Data were collected on gender, age, ethnicity, comorbidities, concomitant medications, type of malignancy, treatments, and renal function. All patients underwent renal biopsy for classification of the mechanism of AKI. Comprehensive genomic profiling (CGP) was performed on tumor tissue for all patients.

Patterns of AKI included acute interstitial nephritis and acute tubular necrosis. Contributing factors included the use of concomitant medications known to contribute to AKI. All but two patients had full resolution of the AKI with the use of steroids. There were several mutations found on CGP that was notable including an Exon 20 insertion as well as multiple NF1 and TP53 mutations. There was high PD-L1 expression on tumor tissue noted in two out of six patients. In addition to AKI, a subset of patients had proteinuria with biopsies revealing corresponding glomerular lesions of minimal change disease and focal and segmental glomerulosclerosis.

Our case series demonstrates that AKI from immune checkpoint inhibitors has a variable presentation that may require an individualized treatment approach. Further studies are needed to identify biomarkers that may help identify those at risk and guide the management of this condition.

Acute interstitial nephritis (AIN) related to immune checkpoint inhibitors (ICI-AIN) has a not completely understood pathophysiology. Our objectives were to analyze possible biomarkers for the differentiation between acute tubular necrosis (ATN) and AIN, especially in cancer patients, and to study the participation of the immune checkpoint pathway in ICI-AIN.

We performed an observational study. We recruited patients with incident diagnosis of ICI-AIN (n = 19). We measured soluble PD-1 (sPD-1), sPD-L1, and sPD-L2 in serum and urine at diagnosis and compared to it patients with non-ICI-related AIN (non-ICI-AIN) (n = 18) and ATN (n = 21). The findings were validated in an independent cohort from another institution (n = 30). Also, we performed PD-L1 and PD-L2 immunostaining of kidney biopsies from patients with ICI-AIN and compared to patients with non-ICI-AIN.

Urinary sPD-1 (usPD-1) was higher in patients with AIN compared to ATN (P = .03). Patients with AIN also showed higher serum sPD-1 (ssPD-1) than patients with ATN (P = .021). In cancer patients, usPD-1 <129.3 pg/ml had a 71.43% sensitivity and 94.44% specificity to differentiate ATN from ICI-AIN, with a likelihood ratio of 12.86. In the external validation cohort, the same cutoff showed a sensitivity of 80%. In kidney biopsies, patients with ICI-AIN showed higher density of PD-L1 positive tubules than patients with non-ICI-AIN (P = .02). The proportion of patients having >2.64/mm2 PD-L2 positive tubules was higher among patients with ICI-AIN compared to non-ICI-AIN (P = .034). There was a positive correlation (P = .009, r = 0.72) between usPD-1 and the number of PD-L1 positive tubules.

UsPD-1 and ssPD-1 are higher in AIN than ATN. Moreover, there was a strong correlation between usPD-1 and renal tubular PD-L1 expression. Our findings suggest a role of usPD-1 as non-invasive biomarker to differentiate ICI-AIN from ATN, especially in cancer patients, which has been confirmed in an external validation cohort.

With the rapid expansion in the development and clinical utility of immune checkpoint inhibitors (ICIs) for oncology, the continual evaluation of the safety profile of such agents is imperative. The safety profile of ICIs as monotherapy is dominated by immune-related adverse events, which can be considered as an extension of the mechanism of action of these immunomodulatory drugs. Further to this, an emerging theme is that ICI treatment can significantly impact upon the tolerability of coadministered medications. Numerous reports in literature indicate that ICIs may alter the immunological perception of coadministered drugs, resulting in undesirable reactions to a variety of concomitant medications. These reactions can be severe in manifestation, including hepatotoxicity and Stevens-Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN), but may also have detrimental impact on malignancy control. To minimize the impact of such drug-drug interactions on patients, it is imperative to identify medications that may cause these reactions, understand the underlying mechanisms, consider the timing and dosing of comedication, and explore alternative medications with comparable efficacies. Improving our understanding of how concomitant medications affect the safety and efficacy of ICIs can allow for potential culprit drugs to be identified/removed/desensitized. This approach will allow the continuation of ICI therapy that may have been discontinued otherwise, thereby improving malignant control and patient and drug development outcomes.

This study aims to figure out the worldwide prevalence of anticancer therapy-associated acute kidney injury (AKI) and tubulointerstitial nephritis (TIN) and the relative risk of each cancer drug. We conducted an analysis of VigiBase, the World Health Organization pharmacovigilance database, 1967-2023 via disproportionate Bayesian reporting method. We further categorized the anticancer drugs into four groups: cytotoxic therapy, hormone therapy, immunotherapy, and targeted therapy. Reporting odds ratio (ROR) and information component (IC) compares observed and expected values to investigate the associations of each category of anticancer drugs with AKI and TIN. We identified 32,722 and 2056 reports (male, n = 17,829 and 1,293) of anticancer therapy-associated AKI and TIN, respectively, among 4,592,036 reports of all-drug caused AKI and TIN. There has been a significant increase in reports since 2010, primarily due to increased reports of targeted therapy and immunotherapy. Immunotherapy exhibited a significant association with both AKI (ROR: 8.92; IC0.25: 3.06) and TIN (21.74; 4.24), followed by cytotoxic therapy (7.14; 2.68), targeted therapy (5.83; 2.40), and hormone therapy (2.59; 1.24) for AKI, and by cytotoxic therapy (2.60; 1.21) and targeted therapy (1.54; 0.61) for TIN. AKI and TIN were more prevalent among individuals under 45 years of age, with a female preponderance for AKI and males for TIN. These events were reported in close temporal relationship after initiation of the respective drug (16.53 days for AKI and 27.97 days for TIN), and exhibited a high fatality rate, with 23.6% for AKI and 16.3% for TIN. These findings underscore that kidney-related adverse drug reactions are of prognostic significance and strategies to mitigate such side effects are required to optimize anticancer therapy.

Brain cancers, particularly glioblastoma multiforme (GBM), are challenging health issues with frequent unmet aspects. Today, discovering safe and effective therapeutic modalities for brain tumors is among the top research interests. Immunotherapy is an emerging area of investigation in cancer treatment. Since immune checkpoints play fundamental roles in repressing anti-cancer immunity, diverse immune checkpoint inhibitors (ICIs) have been developed, and some monoclonal antibodies have been approved clinically for particular cancers; nevertheless, there are significant concerns regarding their efficacy and safety in brain tumors. Among the various tools to modify the immune checkpoints, phytochemicals show good effectiveness and excellent safety, making them suitable candidates for developing better ICIs. Phytochemicals regulate multiple immunological checkpoint-related signaling pathways in cancer biology; however, their efficacy for clinical cancer immunotherapy remains to be established. Here, we discussed the involvement of immune checkpoints in cancer pathology and summarized recent advancements in applying phytochemicals in modulating immune checkpoints in brain tumors to highlight the state-of-the-art and give constructive prospects for future research.

Acute interstitial nephritis (AIN) is a complication of drugs that may cause permanent kidney injury. AIN has been reported in patients with inflammatory bowel disease (IBD) treated with the integrin inhibitor vedolizumab. Through systematic review of existing literature, we aimed to identify and describe cases of AIN in patients with IBD treated with vedolizumab.

We searched Medline, Embase, Cochrane, and Web of Science Core Collection between 1 January 2009 and 25 April 2023. The search yielded 1473 publications. Titles and abstracts were screened by two independent reviewers. Seventy publications were reviewed in full-text. Eight met the inclusion criteria. Clinical characteristics of AIN cases were extracted. Case causality assessment was performed according to two international adverse drug reaction probability assessment scales. Results were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Nine biopsy-confirmed cases of AIN were reported in six patients with ulcerative colitis and three with Crohn's disease. Mean age at AIN onset was 36 years (range = 19-58) and the majority of patients were females (n = 6/9). Time from vedolizumab treatment initiation to AIN onset spanned from hours to 12 months. Common symptoms were fever and malaise. Creatinine levels were elevated in all patients. Five patients sustained permanent kidney injury.

Our findings suggest that vedolizumab, although rarely, could cause AIN in patients with IBD. Awareness of laboratory findings and symptoms consistent with AIN, along with monitoring of the kidney function, could be warranted in patients with IBD treated with vedolizumab.

This study aims to conduct a detailed bibliometric and visual analysis of acute kidney injury (AKI) and immune-related research conducted over the past two decades, focusing on identifying emerging trends and key areas of interest.

The Web of Science Core Collection (WoSCC) was utilised for the meticulous examination of various parameters including publication volume, authorship, geographic distribution, institutional contributions, journal sources, prevalent keywords and citation frequencies. Data were intricately visualised and interpreted using VOSviewer, CiteSpace and Excel 365 software.

Analysis of the WoSCC database revealed 3,537 articles on AKI and immunisation, originating from 94 countries and regions, involving 3,552 institutions and authored by 18,243 individuals. Notably, the top five countries contributing to this field were the United States, China, Germany, Italy and the United Kingdom, with the United States leading with 35.76% of total publications. Among the 3,552 contributing institutions, those in the United States were predominant, with Harvard University leading with 134 papers and 3,906 citations. Key journals driving productivity included Frontiers in Immunology, Kidney International, Journal of the American Society of Nephrology and International Journal of Molecular Sciences, with Kidney International being the most cited, followed by Journal of the American Society of Nephrology and New England Journal of Medicine. Prominent authors in the field included Ronco Claudio, Okusa Mark D and Anders, Hans-Joachim. Co-citation clustering and timeline analysis highlighted recent research foci such as COVID-19, immune checkpoint inhibitors, regulated necrosis, cirrhosis and AKI. Keyword analysis identified "inflammation," "ischaemia-reperfusion injury," "sepsis," "covid-19," and "oxidative stress" as prevalent terms.

This study provides the first bibliometric analysis of AKI and immune research, offering a comprehensive overview of research hotspots and evolving trends within the field.

Introduction: To clarify the prevalence of adverse renal outcomes following targeted therapies in renal cell carcinoma (RCC). Methods: A systematic search was performed in MEDLINE, EMBASE, and Cochrane Central Library. Studies that had reported adverse renal outcomes following targeted therapies in RCC were eligible. Outcomes included adverse renal outcomes defined as either renal dysfunction as evidenced by elevated serum creatinine levels or the diagnosis of acute kidney injury, or proteinuria as indicated by abnormal urine findings. The risk of bias was assessed according to Cochrane handbook guidelines. Publication bias was assessed using Funnel plot analysis and Egger Test. Results: The occurrences of the examined outcomes, along with their corresponding 95% confidence intervals (CIs), were combined using a random-effects model. In all, 23 studies including 10 RCTs and 13 observational cohort studies were included. The pooled incidence of renal dysfunction and proteinuria following targeted therapies in RCC were 17% (95% CI: 12%-22%; I2 = 88.5%, p < 0.01) and 29% (95% CI: 21%-38%; I2 = 93.2%, p < 0.01), respectively. The pooled incidence of both types of adverse events varied substantially across different regimens. Occurrence is more often in polytherapy compared to monotherapy. The majority of adverse events were rated as CTCAE grades 1 or 2 events. Four studies were assessed as having low risk of bias. Conclusion: Adverse renal outcomes reflected by renal dysfunction and proteinuria following targeted therapies in RCC are not uncommon and are more often observed in polytherapy compared to monotherapy. The majority of the adverse events were of mild severity. Systematic Review Registration: Identifier CRD42023441979.

Immune checkpoint inhibitor (ICPi) combined with anti-vascular endothelial growth factor (VEGF) therapy has increasingly become a promising strategy in various malignancies. However, the combination might be associated with increased risk of nephrotoxicity.

We retrospectively recruited patients who suffered kidney injury and received renal biopsy after anti-VEGF/ICPi mono- or combination therapy and divided them into three groups: anti-VEGF monotherapy, ICPi monotherapy and combination therapy. Clinical and histopathological features of three groups were analysed. All patients were followed-up for 3 months after biopsy, with or without glucocorticoid treatment, and renal outcome were compared.

A total of 46 patients were enrolled. Eighteen patients received anti-VEGF monotherapy, 12 received ICPi monotherapy and 16 received combined treatment of anti-VEGF and ICPi. Proteinuria level of anti-VEGF group, ICPi group and combination group were 4.07±3.17 g/day, 0.60±0.61 g/day and 2.05±2.50 g/day, respectively (p=0.002). The peak serum creatinine level of combination group (1.75±0.77 mg/dL) was also in between ICPi group (2.79±0.90 mg/dL) and anti-VEGF group (1.34±0.60 mg/dL) (p<0.001). Multiple histopathological patterns involving glomerulus, tubulointerstitium and vessel existed in the majority of cases in combination group (68.8%). Renal complete and partial recovery rate of combination therapy were also in between monotherapy (57.1% vs 40.0% in anti-VEGF group, 100.0% in ICPi group, respectively).

Kidney injury in patients treated with combination therapy of ICPi and anti-VEGF shows hybrid pathological patterns and intermediate clinical features compared with monotherapy. Cohorts with larger sample and better design, as well as basic research, are needed to elucidate the mechanism of 'protection' effect of combination anti-cancer therapy to renal function.

T cells mediate organ injury and repair. A proportion of unconventional kidney T cells called double-negative (DN) T cells (TCR+ CD4- CD8-), with anti-inflammatory properties, were previously demonstrated to protect from early injury in moderate experimental acute kidney injury (AKI). However, their role in repair after AKI has not been studied. We hypothesized that DN T cells mediate repair after severe AKI. C57B6 mice underwent severe (40 min) unilateral ischemia-reperfusion injury (IRI). Kidney DN T cells were studied by flow cytometry and compared with gold-standard anti-inflammatory CD4+ regulatory T cells (Tregs). In vitro effects of DN T cells and Tregs on renal tubular epithelial cell (RTEC) repair after injury were quantified with live-cell analysis. DN T cells, Tregs, CD4, or vehicle were adoptively transferred after severe AKI. Glomerular filtration rate (GFR) was measured using fluorescein isothiocyanate (FITC)-sinistrin. Fibrosis was assessed with Masson's trichrome staining. Profibrotic genes were measured with qRT-PCR. Percentages and the numbers of DN T cells substantially decreased during repair phase after severe AKI, as well as their activation and proliferation. Both DN T cells and Tregs accelerated RTEC cell repair in vitro. Post-AKI transfer of DN T cells reduced kidney fibrosis and improved GFR, as did Treg transfer. DN T cell transfer lowered transforming growth factor (TGF)β1 and α-smooth muscle actin (αSMA) expression. DN T cells reduced effector-memory CD4+ T cells and IL-17 expression. DN T cells undergo quantitative and phenotypical changes after severe AKI, accelerate RTEC repair in vitro as well as improve GFR and renal fibrosis in vivo. DN T cells have potential as immunotherapy to accelerate repair after AKI.NEW & NOTEWORTHY Double-negative (DN) T cells (CD4- CD8-) are unconventional kidney T cells with regulatory abilities. Their role in repair from acute kidney injury (AKI) is unknown. Kidney DN T cell population decreased during repair after ischemic AKI, in contrast to regulatory T cells (Tregs) which increased. DN T cell administration accelerated tubular repair in vitro, while after severe in vivo ischemic injury reduced kidney fibrosis and increased glomerular filtration rate (GFR). DN T cell infusion is a potential therapeutic agent to improve outcome from severe AKI.

Immune checkpoint inhibitors (ICIs) can provide survival benefits to cancer patients; however, they sometimes result in the development of renal immune-related adverse events (irAEs). Tubulointerstitial nephritis (TIN) is the most representative pathological feature of renal irAEs. However, the clinicopathological entity and underlying pathogenesis of ICI-induced TIN are unclear. Therefore, we compared the clinical and histological features of this condition with those of non-ICI drug-induced TIN. Age and C-reactive protein levels were significantly higher in ICI-induced TIN, but there were no significant differences in renal function. Immunophenotyping of ICI-induced TIN showed massive T cell and macrophage infiltration with fewer B cells, plasma cells, neutrophils, and eosinophils. Compared with those in non-ICI drug-induced TIN, CD4+ cell numbers were significantly lower in ICI-induced TIN but CD8+ cell numbers were not significantly different. However, CD8/CD3 and CD8/CD4 ratios were higher in ICI-induced TIN. Moreover, CD25+ and FOXP3+ cells, namely regulatory T cells, were less abundant in ICI-induced TIN. In conclusion, T cell, B cell, plasma cell, neutrophil, and eosinophil numbers proved useful for differentiating ICI-induced and non-ICI drug-induced TIN. Furthermore, the predominant distribution of CD8+ cells and low accumulation of regulatory T cells might be associated with ICI-induced TIN development.

Kidney cancer (KC) is a disease with a rising worldwide incidence estimated at 400 000 new cases annually, and a worldwide mortality rate approaching 175 000 deaths per year. Current projections suggest incidence continuing to increase over the next decade, emphasizing the urgency of addressing this significant global health trend. Despite the overall increases in incidence and mortality, striking social disparities are evident. Low- and middle-income countries bear a disproportionate burden of the disease, with higher mortality rates and later-stage diagnoses, underscoring the critical role of socioeconomic factors in disease prevalence and outcomes. The major risk factors for KC, including smoking, obesity, hypertension and occupational exposure to harmful substances, must be taken into account. Importantly, these risk factors also often contribute to kidney injury, a condition that the review identifies as a significant, yet under-recognized, precursor to KC. Finally, the indispensable role of nephrologists is underscored in managing this complex disease landscape. Nephrologists are at the forefront of detecting and managing kidney injuries, and their role in mitigating the risk of KC is becoming increasingly apparent. Through this comprehensive analysis, we aim to facilitate a more nuanced understanding of KC's epidemiology and determinants providing valuable insights for researchers, clinicians and policymakers alike.

We are witnessing a revolution in the treatment of metastatic renal cell carcinoma (mRCC). Indeed, several immune-based combinations (ICI [immune checkpoint inhibitor] + ICI, or ICI + antiangiogenic agents) have been approved as first-line therapy for mRCC after demonstrating superior efficacy over the previous standard. Despite all the improvements made, safety remains a critical issue, adverse events (AEs) being the main reason for drug discontinuations or dose reductions, ultimately resulting in an increased risk of losing efficacy. Thus, a good understanding of the AEs associated with the use of immune-based combinations, their prevention, and management, are key in order to maximize therapeutic effectiveness. Among these AEs, renal ones are relatively frequent, but always difficult to be diagnosed, not to take into account that it is often difficult to determine which drug is to blame for such toxicities. Chronic kidney disease (CKD) is a common finding in patients with RCC, either as a pre-existing condition and/or as a consequence of cancer and its treatment; furthermore, CKD, especially in advanced stages and in patients undergoing dialysis, may influence the pharmacokinetics and pharmacodynamics properties of anticancer agents. Finally, managing cancer therapy in kidney transplanted patients is another challenge. In this review, we discuss the therapy management of immune-based combinations in patients with CKD, on dialysis, or transplanted, as well as their renal toxicities, with a focus on their prevention, detection and practical management, taking into account the crucial role of the consulting nephrologist within the multidisciplinary care of these patients.

Acute kidney injury (AKI) has emerged as an important toxicity among patients with advanced cancer treated with immune checkpoint inhibitors. The aim of this study was to describe the incidence, risk factors and mortality of AKI in patients receiving immune checkpoint inhibitors alone or in combination with another form of immunotherapy or chemotherapy.

We included all patients who received immune checkpoint inhibitors alone or in combination with another form of immunotherapy or chemotherapy at AC Camargo Cancer Center from January 2015 to December 2019. AKI was defined as a ≥ 1.5 fold increase in creatinine from baseline within 12 months of immune checkpoint inhibitor initiation. We assessed the association between baseline demographics, comorbidities, medications and risk of AKI using a competing risk model, considering death as a competing event.

We included 614 patients in the analysis. The mean age was 58.4 ± 13.5 years, and the mean baseline creatinine was 0.8 ± 0.18 mg/dL. AKI occurred in 144 (23.5%) of the patients. The most frequent AKI etiologies were multifactorial (10.1%), hemodynamic (8.8%) and possibly immunotherapy-related (3.6%). The likelihood of AKI was greater in patients with genitourinary cancer (sHR 2.47 95% CI 1.34-4.55 p < 0.01), with a prior AKI history (sHR 2.1 95% CI 1.30-3.39 p < 0.01) and taking antibiotics (sHR 2.85 95% CI 1.54-5.27 p < 0.01).

In this study, genitourinary cancer, previous AKI and antibiotics use were associated with a higher likelihood of developing AKI.

The primary objective of this paper is to investigate the research hotspots and future trends of immune-related adverse events induced by immune checkpoint inhibitors, offering valuable insights for researchers in this field.

Using the visual analysis software, this study conducted quantitative statistics and visualization research on the relevant literature concerning immune-related adverse events caused by immune checkpoint inhibitors in the Web of Science Core Collection Database. By evaluating the publication trends, countries, institutions, keywords, research status, cited documents, and document co-citations, among several others, the discussion revolved around the hot spots and future development trends in this field and provided references for future research.

A total of 514 English articles were included, and the top three countries in the research field at the time of this study were the United States, Japan, and China. More specifically, the University of Texas MD Anderson Cancer Center, Dana-Farber Cancer Institute, and Massachusetts General Hospital have been the top three research institutes with more than 10 publications. The frequency of keyword use linked to immune-related adverse events caused by immune checkpoint inhibitors in literature research has been steadily growing over the years. Additionally, the research with respect to the disease focuses on melanoma, cell lung cancer, hepatocellular carcinoma, and breast cancer. In the context of drugs, cancer-related research has mainly focused on the combined use of nivolumab, pembrolizumab, ipilimumab, and immune checkpoint inhibitors. Meanwhile, research on adverse events has delved into the immune checkpoint inhibitors causing vitiligo, thyroid dysfunction, pancreatitis, cholangitis, and rheumatism. Related studies cover acute arthritis, myositis, acute kidney injury, as well as the combination therapy of immune checkpoint inhibitors and docetaxel, management of irAEs in cancer immunotherapy, and biomarkers of immune adverse reactions of immune checkpoint inhibitors. Finally, case report studies of immune adverse reactions caused by immune checkpoint inhibitors could serve as research hotspots in the future.