The emergence of immuno-oncology (IO) has led to revolutionary changes in the field of cancer treatment. Despite notable advancements in this field, a thorough exploration of its full depth and extent has yet to be performed. This study provides a comprehensive overview of publications pertaining to IO. Publications on IO from 2014 to 2023 were retrieved by searching the Web of Science Core Collection database (WoSCC). VOSviewer software and Citespace software were used for the visualized analysis. A total of 1,874 articles have been published in the IO domain. The number of publications and citations has been increasing annually. This study also examines the primary research directions within the field of IO. In conclusion, this study offers a comprehensive overview of the opportunities and challenges associated with IO, illuminating the current status of research and indicating potential future trajectories in this rapidly progressing field. This study provides a comprehensive survey of the current research status and hot spots within the field of IO. It will assist researchers in comprehending the current research emphasis and development trends in this field and offers guidance for future research directions.

Immune checkpoint inhibitors (ICIs) have become an important treatment option for patients with nasopharyngeal carcinoma. With the increasing use of such agents, immune-related adverse events (irAEs) have become a concern. Identifying and managing the toxicity and side effects of ICIs is crucial, since it not only has implications for their safety but also the intensity and efficacy of subsequent use by patients. The present case report documents a 40-year-old male patient with acute erosive hemorrhagic gastritis associated with sintilimab treatment. In particular, the clinical manifestations, treatment, side effects and prognosis of this case was focused upon. The patient was diagnosed with locally advanced nasopharyngeal carcinoma (cT4N3M0 stage IVa) and developed bone metastases after 1 year of standard radiotherapy and adjuvant chemotherapy. After the first- and second-line treatments, pulmonary metastases occurred and sintilimab monotherapy was used as the third-line therapy. During the course of treatment, the optimal outcome for this patient was partial response according to the Response Evaluation Criteria in Solid Tumors (version 1.1). However, after 14 cycles of sintilimab the patient developed melena and epigastric pain and was diagnosed with acute erosive hemorrhagic gastritis, which was treated with methylprednisolone therapy. Progression-free survival with the third-line treatment was 542 days. Sintilimab-associated hemorrhagic gastritis is not fully recognized as an irAE. Therefore, early identification, diagnosis and management of irAEs are critical for subsequent therapy and progression-free survival of patients.

Immune checkpoint inhibitor-induced type 1 diabetes mellitus (ICI-T1DM) is a rare adverse reaction associated with durvalumab. Among the adverse reactions to durvalumab, the incidence of new-onset diabetes is relatively rare, occurring in ~0.2% of cases. The present study reports the case of a 62-year-old woman who developed ICI-T1DM following two cycles of durvalumab, presenting with thirst, polydipsia and polyuria. Laboratory examinations (glycated hemoglobin and glutamic acid decarboxylase antibody), along with consultations from an endocrinologist, led to the patient being diagnosed with ICI-T1DM. Immunotherapy was discontinued, and insulin replacement therapy was initiated. Blood glucose levels were closely monitored using a subcutaneous meter. The onset of diabetic ketoacidosis (DKA) was prevented due to timely treatment. In conclusion, medical oncologists need to be aware that durvalumab, an immunotherapy agent, can induce ICI-T1DM. Therefore, regular monitoring of blood glucose levels and collaborative consultations with endocrinologists are essential for an accurate diagnosis when elevated blood sugar levels are detected. The prompt diagnosis of ICI-T1DM is crucial to prevent the occurrence of DKA.

Immune checkpoint inhibitor-related interstitial pneumonia (CIP) poses a diagnostic challenge due to its radiographic similarity to other pneumonias. We developed a non-invasive model using CT imaging to differentiate CIP from other pneumonias (OTP).

We analyzed CIP and OTP patients after the immunotherapy from five medical centers between 2020 and 2023, and randomly divided into training and validation in 7:3. A radiomics model was developed using random forest analysis. A new model was then built by combining independent risk factors for CIP. The models were evaluated using ROC, calibration, and decision curve analysis.

A total of 238 patients with pneumonia following immunotherapy were included, with 116 CIP and 122 OTP. After random allocation, the training cohort included 166 patients, and the validation included 72 patients. A radiomics model composed of 11 radiomic features was established using the random forest method, with an AUC of 0.833 for the training cohort and 0.821 for the validation. Univariate and multivariate logistic regression analysis revealed significant differences in smoking history, radiotherapy history, and radiomics score between CIP and OTP (p < 0.05). A new model was constructed based on these three factors and a nomogram was drawn. This model showed good calibration and net benefit in both the training and validation cohorts, with AUCs of 0.872 and 0.860, respectively.

Using the random forest method of machine learning, we successfully constructed a CT-based radiomics CIP differential diagnostic model that can accurately, non-invasively, and rapidly provide clinicians with etiological support for pneumonia diagnosis.

The benefits and harms of immune checkpoint inhibitor (ICI) therapy for lung cancer vary across groups, including those typically underrepresented in randomized clinical trials.

To quantify the harms and benefits of ICI-containing regimens in individuals with non-small cell lung cancer and assess heterogeneity across priority subgroups.

This retrospective cohort study conducted in 2024 used 2013 to 2019 Surveillance, Epidemiology, and End Results (SEER) Medicare data of individuals 66 years or older with non-small cell lung cancer who were exposed to any ICI.

ICI + chemotherapy, single ICI (reference group).

Severe immune-related adverse events (irAE; harm) and mortality (when delayed mortality was the benefit). Severe irAEs were defined using validated diagnosis and medication codes. Mortality was ascertained from Medicare data. Hazard ratios (HRs) were estimated and 95% CIs were stratified by whether an ICI was used as the first or second or later systemic anticancer treatment (SACT) and in subgroups defined by preexisting autoimmune disease, sex, and age. The harm-benefit tradeoff was described as excess severe irAEs per year of life gained in which the gain in survival time was assessed using restricted mean survival time.

Of 17 681 Medicare beneficiaries, 8797 (49.5%) were female, and the mean (SD) age was 74 (6.0) years. Compared with a single ICI (14 249 [80.6%]), individuals treated with ICI + chemotherapy (3432 [19.4%]) had an elevated risk of severe irAE in the first SACT setting (hazard ratio [HR], 1.18; 95% CI, 1.06-1.30) but not in the second or later SACT setting (HR, 1.04; 95% CI, 0.92-1.19); there was a decreased risk of mortality in the first SACT setting (HR, 0.66; 95% CI, 0.62-0.72) but not in the second or later SACT setting (HR, 0.94; 95% CI, 0.68-1.03). In the first SACT setting, ICI + chemotherapy delayed mortality more among patients with (vs without) autoimmune disease at baseline. For each 1 year of life gained, the risk of severe irAEs was 0.31 (95% CI, 0.09-0.53) and the tradeoff was also statistically significant in men and patients without autoimmune disease.

The results of this cohort study suggest that given both treatment-related harms and benefits, ICI + chemotherapy use in the first SACT setting requires informed decision-making; the potential benefits of ICI + chemotherapy vs single ICI in high-risk subgroups is encouraging.

With recent breakthroughs in immunotherapy, particularly with the approval of immune checkpoint inhibitors for various cancer indications, patients now have a wider array of treatment options, even for those with metastatic disease. Still, the survival benefit of immune-checkpoint inhibitors is modest, and there is concern about drug toxicity. In addition, there is ongoing exploration into combination therapy involving immune-checkpoint inhibitors, which come at the risk of increased toxicity. Unfortunately, due to the cost of the currently approved doses and dosing intervals, many patients in the community in the United States and low- and middle-income countries lack access to these transformative therapies. Further, the observation of resistance to immune-checkpoint inhibitors and limitations of currently approved doses and dosing intervals warrants changes in current practice. This review paper discusses both model-based and clinical studies in the current literature. Strategies for improving access to immune-checkpoint inhibitors and expanding their utilization, including weight-based dosing instead of fixed dosing, dose and dose interval adjustments, development of biomarkers and scoring systems for personalization of immune-checkpoint inhibitors, and alternative trial design, are discussed.

Melanoma is the main cause of skin cancer-related death. Treatment with immune checkpoint inhibitors (CPI) has improved the prognosis in recent years. However, subtypes of melanoma differ in their response. Acral lentiginous melanoma (ALM) has a worse prognosis compared to cutaneous melanoma other than ALM (CM) and is therefore of particular relevance.

To evaluate the efficacy of CPI in first-line treatment of patients with advanced ALM compared CM.

Retrospective analysis of patients with metastatic ALM (n = 45) or CM (n = 328) who received first-line CPI therapy from the multicenter prospective skin cancer registry ADOREG. Study endpoints were best overall response (BOR), progression-free survival (PFS) and overall survival (OS).

ALM patients had significantly higher rates of ulcerated tumors, loco regional metastases and fewer BRAF-mutated tumors compared to CM patients. Combined CPI was administered in 48.9 % ALM patients and 39.3 % of CM patients, while the remaining patients received PD-1 monotherapy. OS trended to be shorter in patients with ALM (18.1 vs. 43.8 months, p = 0.10) with no significant differences in PFS (7.0 vs. 11.5 months, p = 0.21). In patients with CM, median OS with combined CPI was not reached, whereas the median OS after PD-1 monotherapy was 37.8 months (p = 0.22). Conversely, in patients with ALM, OS with combined CPI was 17.8 months, compared to 26 months with PD-1 monotherapy (p = 0.15). There were no significant differences in BOR between patients with ALM or CM.

Analysis of this real-world cohort of patients with metastatic melanoma showed a trend towards poorer survival outcomes upon first-line treatment with CPI in ALM compared to cutaneous melanoma of other subtypes.

BRAF/MEK inhibitors (BRAFi/MEKi) and PD-1 and CTLA-4 immune checkpoint inhibitors (ICI) have revolutionized malignant melanoma treatment and improved patients' clinical outcome significantly. However, these therapies are associated with substance class-specific side effects. Here, selected cases indicate a correlation between the incidence of mesenteric panniculitis (MP) and BRAFi/MEKi treatment. As MP can mimic or conceal underlying malignancy, the aim of the present study was to confirm a potential correlation with BRAFi/MEKi or ICI in a retrospective, observational analysis of melanoma patients.

In a monocentric retrospective study, abdominal CTs of 490 melanoma patients receiving first-line treatment with ICI (nivolumab, ipilimumab, pembrolizumab, nivolumab/ipilimumab) or BRAFi/MEKi (dabrafenib/trametinib, vemurafenib/cobimetinib, encorafenib/binimetinib) in the adjuvant or advanced situation were evaluated for MP development comparing baseline imaging prior therapy start and follow-up imaging under therapy. MP was defined as an unilocular mesenteric mass characterized by small tissue nodules with increased density of the adjacent fat and a surrounding pseudo-capsule.

384 melanoma patients with ICI (161 women, median age at therapy start: 62 years, IQR: 21 years) and 106 patients with BRAFi/MEKi first-line therapy (46 women, median age: 58 years, IQR: 18 years) were evaluated. MP incidence was significantly higher following BRAFi/MEKi treatment compared to ICI (7.5% vs. 2.9%, p = 0.04). No significance was detected comparing time until MP development from therapy start (174 days, IQR: 518 days [BRAFi/MEKi] vs. 207 days, IQR: 298 days [ICI], p > 0.05).

Our study demonstrates a significant increase in MP development following BRAFi/MEKi treatment compared to ICI in patients with melanoma. As this benign condition can mimic or even conceal malignancy, awareness of its appearance is important.

Question BRAF/MEK and immune checkpoint inhibitors have revolutionized melanoma treatment but are associated with various side effects, yet data regarding the development of mesenteric panniculitis are scarce. Findings BRAF/MEK inhibitor treatment is associated with a significantly higher rate of mesenteric panniculitis compared to immune checkpoint inhibitor treatment in advanced melanoma. Clinical relevance BRAF/MEK inhibitor-treated patients are at risk for development of mesenteric panniculitis. As this benign finding can mimic or conceal malignancy, awareness of it is important especially in these patients.

Tissue-resident memory T (TRM) cells are well reported as a strong protective first line of defense against foreign antigens in non-lymphoid tissues. Moreover, TRM cells have demonstrated critical protective roles in antitumor immunity, contributing to enhanced survival and tumor growth inhibition across various cancer types. However, surprisingly, recent studies suggest that TRM cells can exhibit paradoxical effects, potentially promoting tumor progression under certain conditions and leading to adverse outcomes during antitumor immune responses. Understanding the complexities of TRM cell functions will enable us to harness their potential in advancing cancer immunotherapy more effectively. Therefore, this review comprehensively investigates the dual roles of TRM cells in different tumor contexts, highlighting their protective functions in combating cancers and their unfavorable potential to exacerbate tumor development. Additionally, we explore the implications of TRM cell behaviors for future cancer treatment strategies, emphasizing the need for further research to optimize the therapeutic exploitation of TRM cells while mitigating their deleterious effects.

Alzheimer's disease (AD) represents the most prevalent form of dementia, characterized by progressive cognitive impairment and chronic neuroinflammation. Immune checkpoint inhibitors (ICIs), including anti-programmed cell death (PD)-1 and anti-PD-L1, signify a revolutionary advancement in cancer treatment by preventing T-cell exhaustion; however, their therapeutic application in AD presents a conundrum. Hypothesis: Recent preclinical studies indicate that PD-1 inhibition in AD mouse models induces an interferon-gamma (IFN-γ)-mediated response, leading to increased recruitment of monocyte-derived macrophages into the brain, enhanced clearance of amyloid-beta (Aβ) plaques, and improved cognitive performance. Nonetheless, this therapeutic effect is counterbalanced by the potential for exacerbated neuroinflammation, as PD-1/PD-L1 blockade may potentiate pro-inflammatory T helper (Th)1 and Th17 responses. In this review, we critically discuss the pertinent pro-inflammatory and neuroprotective facets of T cell biology in the pathogenesis of AD, emphasizing the potential for modulation of the PD-1/PD-L1 axis to influence both Aβ clearance and the dynamics of neuroinflammatory processes. In summary, we determine that ICIs are promising tools for reducing AD pathology and improving cognition. However, it is essential to refine treatment protocols and carefully select patients to optimize neuroprotective effects while adequately considering inflammatory risks.

Ophthalmic immune-related adverse events (Eye-irAEs) from immune checkpoint inhibitors can cause visual morbidity. The absence of standardized definitions for Eye-irAEs not only impedes the development of evidence-based treatments but also progress in translational research. The objective of this study was to develop consensus guidance for an approach to Eye-irAEs.Four ophthalmic physicians (uveitis specialists and neuro-ophthalmologists) drafted Eye-irAE consensus guidance and definitions, which were reviewed by the multidisciplinary Eye-irAE definition panel. The panel was divided into Group A (Neuro-ophthalmology/Orbital Disease) and Group B (Uveitis/Ocular Surface Disease). A modified Delphi consensus process was used, with two rounds of anonymous ratings by panelists and two meetings to discuss areas of controversy. For each disorder, five diagnostic components were evaluated: symptoms, examination findings, laboratory studies/imaging findings, diagnostic criteria, and treatment. Panelists rated content for usability, appropriateness and accuracy on 9-point scales in electronic surveys and provided free-text comments. Aggregated survey responses were incorporated into revised definitions. Consensus was based on numeric ratings using the RAND Corporation/ University of California Los Angeles Health Services Utilization Study (RAND/UCLA) Appropriateness Method with prespecified definitions.29 panelists from 25 academic medical centers voted on 114 rating scales (66 neuro-ophthalmic/orbital disease components, 48 uveitis/ocular surface disease components); of these, 86.3% (57/66) in Group A and 89.6% (43/48) in Group B reached first-round consensus. After revisions, all items except 6.1% (4/66) in Group A and 1.6% (1/60) in Group B received second-round consensus. Consensus definitions were achieved for 10/11 neuro-ophthalmic/orbital disorders: optic neuritis, inflammatory optic disc edema, arteritic ischemic optic neuropathy, optic perineuritis, orbital inflammation, thyroid eye disease-like orbital inflammation, cavernous sinus syndrome, oculomotor mononeuritis, trochlear mononeuritis, and abducens mononeuritis. Consensus definitions were achieved for 9/10 uveitis/ocular surface disorders: anterior uveitis, intermediate uveitis, posterior uveitis, panuveitis, Vogt-Koyanagi-Harada-like syndrome, sarcoidosis-like syndrome, acute macular neuroretinopathy, dry eye disease, and scleritis.These disease definitions establish a standardized classification for Eye-irAE, highlighting differences between irAEs and other inflammatory disorders. Importantly, diagnostic certainty does not always align directly with the need to treat as an Eye-irAE. Given the consensus from this representative panel group, it is anticipated the definitions will be used broadly across clinical and research settings.

Since the introduction of immunotherapy and targeted therapies, patients not only have adequate tumoral response to these treatments, but their quality of life has improved due to milder toxicities. However, due to their wide mechanisms of action, the toxicity profile for these therapies is broad, can have an insidious onset, and their recognition can be challenging. Rarely, some of these toxicities can cause significant morbidity if not diagnosed early and lead to intensive care unit (ICU) admission and death. Anesthesiologists are likely to encounter not only a wide spectrum of these toxicities but also a wide range of severity. In some cases, they could be the first to make the diagnosis and therefore need to be prepared to rapidly assess, establish differentials, perform a diagnostic workup, and evaluate the impact the toxicity could have on the patients' care during the perioperative period. In this article, we set to review toxicities of novel cancer therapies such as checkpoint inhibitors and targeted therapies, that could present in the perioperative setting. This article will help as a guide for anesthesiologists to recognize their clinical presentation, the approach to their diagnosis, and their impact on patient care.

Antigen discovery technologies have largely focused on major histocompatibility complex (MHC) class I-restricted human T cell receptors (TCRs), leaving methods for MHC class II-restricted and mouse TCR reactivities relatively undeveloped. Here we present TCR mapping of antigenic peptides (TCR-MAP), an antigen discovery method that uses a synthetic TCR-stimulated circuit in immortalized T cells to activate sortase-mediated tagging of engineered antigen-presenting cells (APCs) expressing processed peptides on MHCs. Live, tagged APCs can be directly purified for deconvolution by sequencing, enabling TCRs with unknown specificity to be queried against barcoded peptide libraries in a pooled screening context. TCR-MAP accurately captures self-reactivities or viral reactivities with high throughput and sensitivity for both MHC class I-restricted and class II-restricted TCRs. We elucidate problematic cross-reactivities of clinical TCRs targeting the cancer/testis melanoma-associated antigen A3 and discover targets of myocarditis-inciting autoreactive T cells in mice. TCR-MAP has the potential to accelerate T cell antigen discovery efforts in the context of cancer, infectious disease and autoimmunity.

Immune checkpoint inhibitors (ICIs) have significantly advanced cancer treatment, but they can also lead to immune-related adverse events (irAEs), including inflammatory arthritis. Understanding the risk factors and underlying mechanisms of irAE pathogenesis is crucial for optimal patient management. Increasing evidence suggests that ICI-mediated activation of tissue-resident memory T cells (TRM) significantly eliminates cancer cells and is associated with irAE-related colitis and dermatitis. However, it remains unknown why the development of these irAEs is restricted to a subset of patients. We hypothesized that osteoarthritis (OA) associated tissue damage and chronic inflammation lead to the recruitment and differentiation of joint TRM cells, predisposing individuals to ICI-induced arthritis.

Using a comprehensive approach, we compared the prevalence of OA in patients with irAE-arthritis to those with irAE non-arthritis and those without irAEs. Additionally, we used advanced immunophenotyping techniques to characterize T-cell populations in the blood and synovial fluid of patients with OA and irAE-arthritis.

Our findings revealed a significantly higher prevalence of OA in patients who developed irAE-arthritis than controls. Furthermore, the multivariable analysis identified OA, body mass index, and smoking as independent risk factors for the development of irAE-arthritis. TRM cells expressing programmed cell death protein-1 (PD-1) were the predominant synovial T cells in OA joints. These cells were directly targeted by ICIs, resulting in an inflammatory immune response and the transition from OA to irAE-arthritis.

This study, the first of its kind, identifies OA as a significant risk factor for irAEarthritis. It reveals a potential mechanism by which ICIs activate PD-1-positive TRM cells in OA joints, resulting in tissue inflammation and irAE-arthritis. This research could significantly enhance the management and treatment of patients with cancer receiving ICIs.

Immunotherapy targeting immune checkpoints has gained traction across various cancer types in clinical settings due to its notable advantages. Despite this, the overall response rates among patients remain modest, alongside issues of drug resistance and adverse effects. Hence, there is a pressing need to enhance immune checkpoint blockade (ICB) therapies. Post-translational modifications (PTMs) are crucial for protein functionality. Recent research emphasizes their pivotal role in immune checkpoint regulation, directly impacting the expression and function of these key proteins. This review delves into the influence of significant PTMs-ubiquitination, phosphorylation, and glycosylation-on immune checkpoint signaling. By targeting these modifications, novel immunotherapeutic strategies have emerged, paving the way for advancements in optimizing immune checkpoint blockade therapies in the future.

Immune checkpoint blockade (ICB) inhibits tumor immune escape and has significantly advanced tumor therapy. However, ICB benefits only a minority of patients treated and may lead to many immune-related adverse events. Therefore, identifying factors that can predict treatment outcomes, enhance synergy with ICB, and mitigate immune-related adverse events is urgently needed.

Tertiary lymphoid structures (TLS) are ectopic lymphoid tissues that arise from the tumor periphery. They have been found to be associated with better prognosis and improved clinical outcomes after ICB therapy. TLS may help address the problems associated with ICB. The multiple mechanisms of action between TLS and ICB remain unknown. This paper described potential mechanisms of interaction between the two and explored their potential applications.

Cancer remains a significant public health issue worldwide, standing as a primary contributor to global mortality, accounting for approximately 10 million fatalities in 2020 [...].

Immune Checkpoint Inhibitors (ICIs) have revolutionized cancer treatment, offering hope for patients with various malignancies. However, along with their remarkable anticancer effects, ICIs can also trigger immune-related adverse events (irAEs). One such noteworthy complication is the development of Diabetes Mellitus (DM), which particularly resembles Type 1 Diabetes Mellitus (T1DM). The aim of this review is to provide insights into the epidemiology, pathophysiology, diagnostic issues, and treatment considerations of ICI-induced DM (ICI-DM), emphasizing the importance of early recognition and management to mitigate adverse outcomes. Although still rare, the incidence has increased with the widespread use of ICIs, especially PD-1/PD-L1 blockers (from 0.2% to 1.9%). Factors affecting the development of ICI-DM, such as specific ICIs, patient demographics, and genetic predispositions, are discussed. The complex interplay between immune dysregulation and pancreatic β-cell destruction contributes to diagnostic challenges, with presentations varying from asymptomatic hyperglycemia to diabetic ketoacidosis (DKA). Management strategies prioritize meticulous glycemic and electrolyte regulation along with tailored intravenous insulin therapy in cases of DKA. DM remission is rare, therefore treatment with both long-acting insulin at bedtime and short-acting insulin before meals is needed in longterm. Total daily insulin requirements can be estimated at 0.3-0.4 units/kg/day for most patients as a starting dose.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. The emergence of programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors offers new therapeutic options for patients with advanced NSCLC, but a comprehensive evaluation of their efficacy and safety is still lacking. In the present study randomized controlled trials (RCTs) published from January 2005 to May 2023 were identified through searches of PubMed, the Cochrane Library and Embase. Analysis focused on 10 PD-1/PD-L1 inhibitors for stages III and IV NSCLC in studies evaluating overall survival (OS), progression-free survival (PFS), the objective response rate, the disease control rate (DCR) and the incidence of severe treatment-related and immune-related adverse events. A total of 37 RCTs involving 31,779 patients were included in the analysis. Compared with chemotherapy, tislelizumab, pembrolizumab and nivolumab all significantly improved OS, with tislelizumab showing the highest probability of being the best treatment for improving OS and DCR. While cemiplimab and tislelizumab had the highest probabilities of improved PFS, no significant differences were observed across all PD-1/PD-L1 inhibitors. Combination therapies, such as nivolumab or cemiplimab with chemotherapy, increased OS and PFS but also increased the incidence of severe treatment-related adverse events. In particular, cemiplimab and pembrolizumab were associated with a greater risk of severe immune-related adverse events. In conclusion, PD-1/PD-L1 inhibitors, especially tislelizumab, pembrolizumab and nivolumab, were effective first-line treatments for NSCLC, providing survival benefits. However, the combination of PD-1/PD-L1 inhibitors with chemotherapy increased the risk of severe adverse events. Further research is needed to optimize treatment strategies.

Sialadenitis is an inflammation of one or more of the salivary glands. A 21-year-old genetic female undergoing combination ipilimumab/nivolumab therapy for metastatic melanoma presented to our hospital with anterior neck swelling. CT imaging demonstrated bilateral submandibular gland sialadenitis. The clinical picture was most consistent with immunotherapy-related sialadenitis, and the patient responded promptly to systemic corticosteroids.

Immune checkpoint inhibitors (ICIs) are associated with an increased risk of major adverse cardiovascular events (MACE). Glucagon-like peptide-1 agonists (GLP1a), initially developed for type 2 diabetes mellitus (T2DM), have shown promising results in reducing cardiovascular events. We aimed to investigate the effect of GLP1a on cardiovascular events in patients receiving ICIs.

We conducted a retrospective, propensity score-matched cohort study using the TriNetX database. We identified adults with cancer and T2DM who received ICIs between April 2013 and May 2023. The primary efficacy outcome was incident MACE, defined as a composite of myocardial infarction, need for coronary revascularization, heart failure, ischemic stroke, and cardiac arrest. The secondary efficacy outcomes were the individual components of MACE as well as myocarditis and pericarditis. Safety outcomes included the occurrence of immune-related adverse events, serious adverse events related to GLP1a use, and all-cause mortality.

We identified 7651 patients eligible for inclusion, among which 479 received GLP1a and 7172 received non-GLP1a diabetes medications. After matching (469 patients each), baseline characteristics were well-balanced. Over a median 12-month follow-up, the GLP1a cohort had a significantly lower MACE incidence than the non-GLP1a cohort (9.0 vs. 17.1 events per 100 patient-years) with a 54 % lower risk of MACE (Hazard ratio (HR),0.46 [95 % CI: 0.32-0.67]). There were reductions in myocardial infarction or need for coronary revascularization, heart failure, and all-cause mortality, with no differences in other cardiovascular events. GLP1a use did not increase risk of adverse events, including pancreatitis, biliary disease, bowel obstruction, gastroparesis, and immune-related adverse events.

GLP1a use in cancer patients with T2DM receiving ICIs was associated with reduced MACE and all-cause mortality without an increased risk in serious adverse events.

Acute respiratory distress syndrome (ARDS) is a clinical syndrome of acute hypoxic respiratory failure caused by diffuse lung inflammation and edema. ARDS can be precipitated by intrapulmonary factors or extrapulmonary factors, which can lead to severe hypoxemia. Patients suffering from ARDS have high mortality rates, including a 28-day mortality rate of 34.8% and an overall in-hospital mortality rate of 40.0%. The pathophysiology of ARDS is complex and involves the activation and dysregulation of multiple overlapping and interacting pathways of systemic inflammation and coagulation, including the respiratory system, circulatory system, and immune system. In general, the treatment of inflammatory injuries is a coordinated process that involves the downregulation of proinflammatory pathways and the upregulation of anti-inflammatory pathways. Given the complexity of the underlying disease, treatment needs to be tailored to the problem. Hence, we discuss the pathogenesis and treatment methods of affected organs, including 2019 coronavirus disease (COVID-19)-related pneumonia, drowning, trauma, blood transfusion, severe acute pancreatitis, and sepsis. This review is intended to provide a new perspective concerning ARDS and offer novel insight into future therapeutic interventions.

Heart failure and cancer remain 2 of the leading causes of morbidity and mortality, and the 2 disease entities are linked in a complex manner. Patients with cancer are at increased risk of cardiovascular complications related to the cancer therapies. The presence of cardiomyopathy or heart failure in a patient with new cancer diagnosis portends a high risk for adverse oncology and cardiovascular outcomes. With the rapid growth of cancer therapies, many of which interfere with cardiovascular homeostasis, heart failure practitioners need to be familiar with prevention, risk stratification, diagnosis, and management strategies in cardio-oncology. This Heart Failure Society of America statement addresses the complexities of heart failure care among patients with active cancer diagnoses and cancer survivors. Risk stratification, monitoring and management of cardiotoxicity are presented across stages A through D heart failure, with focused discussion on heart failure with preserved ejection fraction and special populations, such as survivors of childhood and young-adulthood cancers. We provide an overview of the shared risk factors between cancer and heart failure, highlighting heart failure as a form of cardiotoxicity associated with many different cancer therapeutics. Finally, we discuss disparities in the care of patients with cancer and cardiac disease and present a framework for a multidisciplinary-team approach and critical collaboration among heart failure, oncology, palliative care, pharmacy, and nursing teams in the management of these complex patients.

Immune checkpoint inhibitors (ICIs), such as pembrolizumab, have revolutionized cancer treatment by enhancing the immune system's response to malignancies. However, these therapies are associated with immune-related adverse events (irAEs), including neuromuscular complications such as myasthenia gravis, myositis, and myocarditis. We describe two male patients, aged 67 and 68, with small cell and non-small cell lung cancers, who developed progressive neuromuscular symptoms, including ptosis, diplopia, and generalized weakness, after receiving pembrolizumab. Clinical, biochemical, imaging, and electrophysiological findings confirmed the diagnosis of myositis with myastheniform features, with one case also involving myocarditis. Both patients underwent treatments with intravenous immunoglobulin (IVIg), pyridostigmine, and corticosteroids. The first patient, despite aggressive treatment including plasma exchange and rituximab, succumbed to complications from aspiration pneumonia. The second patient showed partial response to pyridostigmine and IVIg but later died due to metastatic cancer progression. A literature review revealed 52 cases of pembrolizumab-associated myositis with myastheniform symptoms, emphasizing its high morbidity and the need for vigilant monitoring. Pembrolizumab-associated myositis with myastheniform symptoms, especially when accompanied by myocarditis, presents a significant clinical challenge with high mortality. Early recognition and aggressive management of these irAEs are crucial to improving outcomes in cancer patients receiving ICIs.

Immune checkpoint inhibitors (ICIs) have significantly changed cancer therapy, improving patient survival rates and clinical outcomes. Nevertheless, the use of PD-1/PD-L1 inhibitors can result in immune-related adverse events (irAEs). This study aims to investigate the prevalence and associated risk factors of irAEs in a real-world setting, as well as to assess their effects on optimal therapeutic outcomes.

A retrospective analysis involved 2523 patients with cancer who received inpatient PD-1/PD-L1 inhibitors treatment between January 2018 and December 2022. We documented patients' demographic and clinical characteristics, PD-1 or PD-L1 inhibitors, treatment modalities, incidences, timing, and severity of irAEs, and efficacy outcomes by reviewing inpatient records. Patients were categorized into an irAEs group and a non-irAEs group, with the former further subdivided into a multiple irAEs group and a single irAE group. Chi-square tests were employed to evaluate differences in baseline characteristics and efficacy outcomes between the irAEs and non-irAEs groups, as well as between the multiple and single irAE groups. Additionally, logistic regression analysis was utilized to identify risk factors linked to irAEs.

Among 2523 eligible patients, 1096 reported 1802 irAEs, with an incidence incidence of 43.4%. Among 1096 individuals, 92.1% were classified as grade 1-2, while 7.9% were grade 3 or higher. IrAEs affected various organ systems, with endocrine toxicity (17.7%), hepatic toxicity (17.2%), and hematologic toxicity (11.4%) being the most common. 20.5% patients experienced multi-system irAEs. The average time for patients to develop irAEs was within four treatment cycles. Significant differences in patient gender, age, Eastern Cooperative Oncology Group (ECOG) Performance Status (PS), comorbidities, PD-1 or PD-L1 inhibitors, and treatment modalities were observed between the irAEs and non-irAEs groups, but not between the multiple irAEs and single irAE groups. Compared to the non-irAEs group, the irAEs group exhibited a higher objective response rate (ORR) and disease control rate (DCR), and the multiple irAEs group also showed a higher ORR than the single irAE group.

This real-world study indicated that the occurrence of irAEs is related to patient gender, age, ECOG PS, comorbidities, PD-1/PD-L1 inhibitors, and treatment modalities. The occurrence of irAEs may be associated with better treatment benefits.

Immune checkpoint inhibitors (ICIs) are emerging treatment options for children with brain tumors, who are already at risk for developing endocrinopathies due to tumor location and treatment. Endocrine ICI-related adverse effects (irAEs) are common in adults but poorly characterized in the pediatric population. The aims of this study were to determine in pediatric brain tumor patients in a single institution (1) if endocrine surveillance took place before and after ICIs were initiated, and (2) the occurrence of endocrine irAEs.

This is a retrospective chart review of 22 pediatric brain tumor patients treated with ICIs at Children's Hospital Los Angeles between 2010 and 2022. We analyzed endocrine laboratory results, patient demographics, and treatment course.

Most patients (82 %) received surveillance in at least one endocrine system before ICI treatment - all had thyroid function tested (100 %) whereas non-thyroid endocrine functions were seldomly assessed (6-22 %). Only those patients with surveillance prior to treatment had ongoing surveillance after ICI initiation - 100 % for thyroid function and 17-39 % for other endocrine systems. Hypothyroidism was the only endocrine problem diagnosed after ICI initiation, in two patients (9 %). Of note, most patients (68 %) expired during or shortly after ICI treatment.

This is one of the first institutional surveys of pediatric ICIs in a high-volume pediatric brain tumor center. Thyroid surveillance commonly occurred in pediatric patients, revealing diagnoses of hypothyroidism, which is consistent with adult data. However, little information is available for non-thyroid endocrine conditions, reflecting the need for comprehensive and systematic endocrine surveillance.

Background/Objectives: Few studies have focused on patients with immune-related adverse events (irAEs) after immune checkpoint inhibitor (ICI) treatment who were cared for primarily by hospitalists. The objective of our study was to describe the patterns and outcomes of adult solid-tumor cancer patients admitted to our onco-hospital medicine service. Methods: We retrospectively reviewed patients with solid tumors who received ICIs and were admitted to our service in 2021-2022 with an irAE and compared them to a control group (IOTOX vs. NO IOTOX, respectively). The primary outcome was the patterns of irAEs requiring hospitalization; secondary outcomes included 30-day emergency room visit, readmission, and 30-day mortality. Results: There were 144 patients in the IOTOX group and 286 controls. The most common tumor type was lung and thoracic malignancies (62, 43.1%). The most common ICI causing the irAEs was pembrolizumab (66, 45.8%). The most common irAEs were pneumonitis (49, 34%), colitis (28, 19.4%), hepatitis (18, 12.5%), and myocarditis (16, 11.1%). Of the 144 patients, eight (6%) died from the hospitalization irAE. Fifteen (15.6%) had an ER visit within 30 days due to the same irAE, and thirteen (13.7%) were readmitted. Survival at 30 days after discharge did not differ significantly between groups. Conclusions: Despite many patients having severe irAEs and irAEs associated with higher mortality, they generally had a favorable outcome compared to the literature.

Multiple Myeloma is a hematological malignancy characterized by the proliferation of clonal plasma cells and associated with severe clinical manifestations. Despite advancements in diagnosis and management, Multiple Myeloma remains incurable, necessitating further research into more effective therapies.

The primary objective of this review is to provide an informative and critical summary of the Multiple Myeloma microenvironment, and emerging revolutionary therapeutic approaches with potential combination therapy to improve the quality of life for Multiple Myeloma patients.

Recent advancements in immunotherapy, particularly immune checkpoint inhibitors (ICIs), have shown improvements in immune response against Multiple Myeloma. ICIs target inhibitory pathways such as PD-1/PD-L1 and CTLA-4, potentially overcoming tumor-induced immunosuppression. Combination therapies integrate ICIs with proteasome inhibitors, immunomodulators, and monoclonal antibodies to enhance the anti-tumor immune response. Additionally, Chimeric Antigen Receptor T-cell (CAR-T) therapy has demonstrated effectiveness against Multiple Myeloma, particularly when coupled with ICIs to decrease resistance and relapse.

Although the efficacy of ICIs in treating Multiple Myeloma has been hindered by the complexity of the tumor microenvironment and immune evasion mechanisms, this challenge has led to the exploration of combination therapies. Potential side effects are still a big challenge for newly recognized ICIs and combination treatment.

Investigations of new immune checkpoints and the development of targeted therapies against these markers are in progress, creating possibilities for more personalized and effective treatment strategies. Continuous research and robust clinical trials are needed to comprehend the complex dynamics of the Multiple Myeloma microenvironment to develop revolutionary therapeutic targets.

The lymphocyte population must traverse a complex path throughout their journey to the liver. The signals which these cells must detect, including cytokines, chemokines and other soluble factors, steer their course towards further crosstalk with other hepatic immune cells, hepatocytes and biliary epithelial cells. A series of specific chemokine receptors and adhesion molecules drive not only the recruitment, migration, and retention of these cells within the liver, but also their localisation. Perturbation of these interactions and failure of self-recognition drives the development of several autoimmune liver diseases. Understanding the nature of these interactions develops our understanding of immune mediated liver disease pathogenesis, providing new opportunities for intervention to resolve uncontrolled inflammation. In this review, we provide an overview of the complex recruitment pathways and cellular interactions which position lymphocyte populations in the liver. We discuss how these are disrupted in autoimmune diseases and highlight the mechanism of immune cells inside hepatocytes (emperipolesis) in autoimmune hepatitis and immune cells inside biliary epithelial cells (intra-epithelial lymphocyte) in primary biliary cholangitis as well as avenues to manipulate these pathways for therapy. We also cover the immune mediated tissue injury mechanisms impacted by checkpoint inhibitors, leading to checkpoint inhibitor-induced liver injury (CHILI). Finally, we describe emerging immune-based therapies, including regulatory T cell, anti-cytokine and anti-chemokine therapies, cytokine supplementation such as interleukin-2 as well as numerous modalities of co-inhibitory molecule manipulation, including bispecific T cell engagers (BiTEs) and checkpoint inhibitor bispecific T cell engagers (CiTEs) and discuss their potential application in the treatment of autoimmune liver diseases. Immune-mediated liver disease encompasses two broad categories: autoimmune and inflammatory liver injury, the former resulting from a breakdown in immunological self-tolerance. These share common features, namely histologically dense immune infiltrates, autoantibody positivity and immunoglobulin elevation. Whilst well defined in their epidemiology, presentation and diagnostic evaluation, their treatment remains an unmet clinical need. Our incomplete understanding of the mechanisms leading to breakdown in immunological self-tolerance and our inability to restore immune homeostasis hampers present progress in treatment. This review summarises recent advances in our understanding of the loss of hepatic tolerance and the cellular interactions leading to this, including immune cell invasion towards hepatocytes and biliary epithelial cells, checkpoint-induced immune-mediated liver injury (CHILI) and concludes with current progress in treatment strategies.

Immune checkpoint inhibitors (ICIs) have revolutionised cancer therapy, yet they carry a unique spectrum of immune-related adverse events (irAEs). Given the ageing global population and the underrepresentation of older adults in clinical trials for ICIs, we investigated the occurrence and characteristics of irAEs in older versus younger adults as well as among different age subsets within the older adult population.

We analysed the U.S. Food and Drug Administration Adverse Event Reporting System database reports from 2015 to 2023, focusing on ICIs. We categorised irAEs into 11 distinct types and performed descriptive and multivariate analyses to compare the prevalence and clinical characteristics of irAEs across different age groups, adjusting for potential confounding factors.

Among 47 513 patients aged 18-100 reporting irAEs, the 65-74 and 75-84 age groups had significantly increased risks compared to 18-64 (OR 1.13, 95% CI [1.09-1.18]; 1.15 [1.1-1.21]). Cardiovascular irAEs rose with age, peaking at 75-84, while endocrine irAEs decreased. Hepatobiliary, gastrointestinal and ocular irAEs decreased with age, but renal and musculoskeletal irAEs increased, showing higher risks in older adults. Serious outcomes slightly decreased in the 85+ group, while the proportion of deaths increased with age.

We discuss the potential changes in the immune system contributing to the decreased prevalence of irAEs in the oldest age group. Additionally, conservative treatment approaches and underreporting of irAEs in older patients may influence these findings. Our findings highlight the need for personalised decision-making for ICI therapies, considering performance status and comorbidities rather than age alone.

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but are frequently associated with immune-related adverse events (irAEs). This article offers a novel synthesis of findings from both preclinical and clinical studies, focusing on the molecular mechanisms driving irAEs across diverse organ systems. It examines key immune cells, such as T cell subsets and myeloid cells, which are instrumental in irAE pathogenesis, alongside an in-depth analysis of cytokine signaling [interleukin (IL)-6, IL-17, IL-4), interferon γ (IFN-γ), IL-1β, tumor necrosis factor α (TNF-α)], integrin-mediated interactions [integrin subunits αITGA)4 and ITGB7], and microbiome-related factors that contribute to irAE pathology. This exploration of modifiable pathways uncovers new opportunities to mitigate irAEs by using available antibodies (Abs) that target key inflammatory molecules across tumor types, while ideally preserving the antitumor efficacy of ICIs.

Immune checkpoint inhibitors (ICIs) are effective treatments for patients with metastatic melanoma, including patients with brain metastasis (BM). However, half of patients with melanoma BM have intracranial progression within 6 months after the start of ICIs. We investigated whether size affects response to ICIs in patients with melanoma BM.

In this single-center cohort study, patients with melanoma BM who were treated with ICIs between 2012 and 2021 were included. Clinical and radiologic features were collected at baseline. Longest axial diameter of all BMs was measured on baseline and follow-up MRI, and segmentation was performed for all BMs on baseline MRI. Lesion-level logistic regression analysis and patient-level survival analysis were performed for early BM progression (ie, within 6 months after start of ICIs) and intracranial progression-free survival (PFS), respectively.

A total of 82 patients were included with a total of 464 BMs. At baseline, 37.8% of patients had ≥ 4 BMs and 53.7% of patients had at least one BM with a diameter ≥ 10 mm. In multivariable analysis on the lesion level, baseline BM diameter was associated with early BM progression (odds ratio 1.10, 95%CI 1.05-1.15, P < .001). On the patient level, having at least one BM ≥ 10mm was associated with shorter intracranial PFS (hazard ratio 2.08, 95%CI 1.64-5.56, P < .001).

Large BM diameter was associated with a higher risk of early progression after the start of ICIs. Therefore, local therapy should be considered for patients who are treated with ICIs and who have melanoma BMs ≥ 10 mm.

Immune checkpoint inhibitors (ICIs) are crucial in cancer treatment, and the associated immune-related adverse events (irAEs) have garnered significant attention, yet reports on associated immune related gastritis are limited. The diagnosis of immune related gastritis remains predominantly exclusionary, meanwhile its management diverges significantly from that of conventional gastritis. Current guidelines lack standardized grading criteria, and substantial data from large-scale, tertiary clinical studies are absent, therefore we conducted a systematic review of Medline, Web of Science, and Embase databases, identifying 31 articles from 2017 to December 31, 2023, involving 258 patients. Clinical manifestations included epigastric pain (53.1%), mucosal erythema (56.1%), and lymphocyte infiltration (48.6%). Corticosteroid therapy was common (94.7%), with 86.7% experiencing post-treatment improvement. 80% of patients can be diagnosed through endoscopy and pathology, while the remaining 20% may require PET-CT. Hormonal therapy is favored but diverges from standard management. Accurate diagnosis is crucial in managing immune related gastritis effectively.

Immune checkpoint inhibitors (ICIs) have been approved for monotherapy and combined therapy with chemotherapy and/or radiotherapy in China since 2018. The number of patients receiving ICIs has significantly increased in recent years, and the collection and analysis of this data are crucial for a comprehensive understanding of their clinical outcomes and adverse effects. The effects of ICIs may vary among different ethnic groups, and there is a lack of such data in the Chinese population. This study aimed to investigate the occurrence rate of various types of immune-related adverse events (irAEs) of ICIs in cancer survivors with different types of cancer and explore the associated risk factors. Demographic data, cancer type, dosage, Eastern Cooperative Oncology Group Performance Score (ECOG-PS), and details of irAEs were collected from 120 participants who underwent ICI treatment. Descriptive statistics were used to summarise the patient population characteristics, while t-tests and Chi-square tests assessed associations between variables. Multiple logistic regression evaluated the relationships between independent variables and the likelihood of experiencing irAEs. The results indicated that the occurrence of less severe G1 and G2 irAEs was 25%, while more severe G3 to G5 irAEs accounted for 5.8% of the total. Among the irAEs, skin toxicity had the highest incidence rate (14.2%), followed by gastrointestinal toxicity (6.7%), and endocrine toxicity had the lowest incidence rate of 2.5%. The multiple logistic regression model revealed that patients with ECOG-PS ≥ 2 are over five times more likely to experience irAEs compared to those with lower ECOG-PS (OR: 5.03, 95% CI: 1.05-24.17). Additionally, patients with cancer stage IV have 11.47 times the odds of experiencing irAEs (OR: 11.47, 95% CI: 1.05-24.17). In conclusion, a substantial proportion of patients receiving ICIs experienced irAEs. Patients with an ECOG-PS score of ≥ 2 and advanced cancer stage are at increased risk for these events, necessitating close monitoring by healthcare professionals. The identification of skin and gastrointestinal toxicities as the most common irAEs revealed the need for targeted education for the patients and their carers to recognise and manage these issues. Furthermore, our findings, in conjunction with existing literature, may guide future research on predictive modelling for high-risk patients receiving ICIs.

Immunotherapy, particularly that based on blocking checkpoint proteins in many tumors, including melanoma, Merkel cell carcinoma, non-small cell lung cancer (NSCLC), triple-negative breast (TNB cancer), renal cancer, and gastrointestinal and endometrial neoplasms, is a therapeutic alternative to chemotherapy. Immune checkpoint inhibitor (ICI)-based therapies have the potential to target different pathways leading to the destruction of cancer cells. Although ICIs are an effective treatment strategy for patients with highly immune-infiltrated cancers, the development of different adverse effects including cutaneous adverse effects during and after the treatment with ICIs is common. ICI-associated cutaneous adverse effects include mostly inflammatory and bullous dermatoses, as well as severe cutaneous side reactions such as rash or inflammatory dermatitis encompassing erythema multiforme; lichenoid, eczematous, psoriasiform, and morbilliform lesions; and palmoplantar erythrodysesthesia. The development of immunotherapy-related adverse effects is a consequence of ICIs' unique molecular action that is mainly mediated by the activation of cytotoxic CD4+/CD8+ T cells. ICI-associated cutaneous disorders are the most prevalent effects induced in response to anti-programmed cell death 1 (PD-1), anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), and anti-programmed cell death ligand 1 (PD-L1) agents. Herein, we will elucidate the mechanisms regulating the occurrence of cutaneous adverse effects following treatment with ICIs.