Locally advanced or metastatic melanoma is a cancer with a poor prognosis, characterised by its ability to respond to the induction of an immune response. Anti-tumour vaccination has been studied for many years, although initial results have sometimes been disappointing. The emergence of immune checkpoint inhibiting immunotherapies has dramatically changed the prognosis. Melanoma has emerged as a prime model for renewed research into anti-tumour vaccination. The aim of this review article is to provide an overview of recent developments and prospects for antigen vaccines in the treatment of melanoma. We will explore their mechanism of action, the results of recent clinical trials, and the limitations and challenges of this new therapeutic approach.

Oral Cancer is one of the most prevalent malignant tumors of the head and neck. The three primary clinical treatments available till now for oral cancer are chemotherapy, radiation, and surgery. The goal of this review was to outline the basic principles of immunotherapy along with various immunotherapeutic agents on Oral Squamous Cell Carcinoma.

A comprehensive search in PubMed, Scopus, and Google Scholar was performed using relevant keywords. All the articles, both English as well as non-English were included also with inclusion data from high-incidence countries (South-east Asia) and the compilation was ten done after getting the data reviewed from two pathologists who were blinded to the data.

All the data has been compiled and the various sections in the manuscript provides an insight into the current trends in immunotherapy.

Advanced research studies are needed to counteract the hurdles associated with immunotherapy so that a greater proportion of patients can be treated.

One of the more recent developments that is promising is immunotherapy, which can be quite beneficial when used as a monotherapy or an adjuvant treatment. This more recent treatment approach could serve as the fourth pillar in cancer care, alongside radiation, chemotherapy, and surgery. Because immunotherapy relies on the patient's immunological environment, careful patient selection is essential to its effectiveness.

Drug resistance, systemic toxicity, low solubility, and rapid clearance are common issues with chemotherapy drugs and other molecules used to treat cancer. The development of new therapeutic compounds and nanotherapy offers a solution to these issues. Therapeutic peptides have attracted great interest among these molecules due to their unique advantages, including low immunogenicity, efficient cellular internalization, deep tissue penetration, and low systemic toxicity. They have shown promise in cancer treatment by inducing apoptosis, necrosis, or cell lysis and promoting immunotherapy. In addition, peptides can deliver a range of cargoes, such as drugs, nucleic acids, imaging agents, and nanoparticles, and can specifically target cancer cells. However, problems such as their short half-life and low solubility limit their therapeutic use. Recent developments have addressed these constraints through structural alterations and nanoparticle formulations. In particular, cholesterol modification makes it possible for peptides to self-assemble into nanomicelles, which enhances their stability, half-life, and cell penetration. In this review, therapeutic peptides are presented as a versatile and successful cancer treatment option. The potential of cholesterol-modified peptide micelles as a reliable drug, nucleic acid, and imaging agent delivery system is also examined.

Endocrine cancer, a relatively rare and heterogeneous tumor with diverse clinical features. The facile synthesis of hormones further complicates endocrine cancer treatment. Thus, the development of safe and effective systemic treatment approaches, such as chimeric antigen receptor (CAR) T cell therapy, is imperative to enhance the prognosis of patients with endocrine cancer. Although this therapy has achieved good results in the treatment of hematological malignancies, it encounters diverse complications and challenges in the context of endocrine cancer. This review delineates the generation of CAR-T cells, examines the potential of CAR-T cell therapy for endocrine cancer, enumerates pivotal antigens linked to endocrine cancer, encapsulates the challenges confronted with CAR-T cell therapy for endocrine cancer, and expounds upon strategies to overcome these limitations. The primary objective is to provide insightful perspectives that can contribute to the advancement of CAR-T cell therapy in the field of endocrine cancer.

Cancer vaccines hold promise for tumor immunotherapy, with their success hinging on effective systems to boost anti-tumor immunity. Biological membranes are not only a delivery vehicle but also a source of antigens and adjuvants, garnering growing interest in vaccine research. This review starts with an introduction to the composition and mechanisms of cancer vaccines and describes the sources, advantages/disadvantages, engineering strategies, and applications of these membrane-based platforms for cancer vaccine development. This review also offers a critical analysis and discusses the further direction of the vaccine platform in view of clinical translation for tumor immunotherapy.

The detection of exosomes is critical for health monitoring and disease diagnosis. However, their small size and low concentration present significant challenges. In this study, we designed a dual-control microchip integrated with a surface-enhanced Raman scattering (SERS) signal amplification detection method. By employing separate chambers for isolation and detection, this method achieves magnetic separation control and DNA cascade signal amplification with electrokinetic enrichment detection. The magnetic separation step captures and isolates exosomes in a magnetic-controlled reaction chamber, releasing a signal-switching strand that translates exosome recognition into a DNA signal amplification process. The DNA cascade reciprocal signal amplification reaction is performed in an electrokinetic enrichment reaction chamber, significantly improving detection efficiency and signal intensity. In addition, absolute-value coupled data processing reduces background interference. These unique merits enable precise and highly efficient assay of exosomes. This dual-control microchip signal amplification sensor exhibits remarkable sensitivity, rapid detection times, with a detection limit of 10.9 particles/μL and a reaction time of 35 min, and successful application to real sample analysis. The platform offers a viable, accurate, and portable solution for medical point-of-care testing.

Since the first approval of an immune checkpoint inhibitor, we have witnessed the clinical success of cancer immunotherapy. Adoptive T-cell therapy with chimeric antigen receptor T (CAR-T) cells has shown remarkable efficacy in hematological malignancies. Concurrently with these successes, the cancer immunoediting concept that refined the cancer immunosurveillance concept underpinned the scientific mechanism and reason for past failures, as well as recent breakthroughs in cancer immunotherapy. Now, we face the next step of issues to be solved in this field, such as tumor heterogeneity, the tumor microenvironment, the metabolism of tumors and the immune system, and personalized approaches for patients, aiming to expand the population benefitted by the therapies.

Ulcerative colitis (UC) is a heterogeneous autoimmune condition. PANoptosis, a new form of programmed cell death, plays a role in inflammatory diseases. This study aimed to identify differentially expressed PANoptosis-related genes (PRGs) involved in immune dysregulation in UC. Three key PRGs-BIRC3, MAGED1, and PSME2 were found using weighted gene co-expression network analysis (WGCNA) and machine learning. Immune infiltration analysis revealed that these key PRGs were associated with neutrophils, CD8+ T cells, activated CD4 T cells, and NK cells. Moreover, these key PRGs were significantly enriched in pathways related to inflammatory bowel disease, the IL-17 signaling pathway, and NOD-like receptor signaling pathway. The expression levels of the key PRGs were validated in various datasets, animal models, and UC intestinal tissue samples. Our findings confirmed the involvement of PANoptosis in UC and predict hub genes and immune characteristics, providing new insights for further investigations into UC pathogenic mechanisms and therapeutic strategies.

Circadian rhythms send messages to regulate the sleep-wake cycle in living beings, which, regulate various biological activities. It is well known that altered sleep-wake cycles affect host metabolism and significantly deregulate the host immunity. The dysregulation of circadian-related genes is critical for various malignancies. One of the hallmarks of cancer is altered metabolism, the effects of which spill into surrounding microenvironments. Here, we review the emerging literature linking the circadian immunometabolic axis to cancer. Small metabolites are the products of various metabolic pathways, that are usually perturbed in cancer. Genes that regulate circadian rhythms also regulate host metabolism and control metabolite content in the tumor microenvironment. Immune cell infiltration into the tumor site is critical to perform anticancer functions, and altered metabolite content affects their trafficking to the tumor site. A compromised immune response in the tumor microenvironment aids cancer cell proliferation and immune evasion, resulting in metastases. The role of circadian rhythms in these processes is largely overlooked and demands renewed attention in the search for targets against cancer growth and spread. The precision medicine approach requires targeting the circadian immune metabolism in cancer.

The melanoma-associated antigen gene (MAGE) is a key target in cancer immunotherapy. Given the potential of MAGE-B genes in veterinary immunotherapy for canine mammary tumors (CMTs), this study investigated the mRNA expression of MAGE-B1, -B4, -B5, and -B10 in CMT tissues and cells from dogs. Quantitative real-time PCR was used to analyze 28 CMT tissue samples, including 4 benign and 24 malignant tumors (13 simple carcinomas, 6 complex carcinomas, 3 carcinosarcomas, and 2 fibrosarcomas). Benign mixed tumor and complex carcinoma-type CMT cells were cultured and treated with a DNA methylase inhibitor (5-aza-2'-deoxycytidine; 5-aza-CdR) and a histone deacetylase inhibitor (Trichostatin A; TSA) under the following four conditions: (1) 5-aza-CdR for 72 h; (2) TSA for 24 h; (3) 5-aza-CdR for 48 h followed by TSA for 24 h; and (4) control. MAGE-B1 and -B4 showed the highest expression in the CMT samples (100% and 89.29%, respectively), followed by MAGE-B10 (82.14%). Carcinosarcomas and simple anaplastic carcinomas had significantly higher MAGE-B expression levels than simple tubulopapillary carcinomas (p < 0.05). 5-aza-CdR treatment increased MAGE-B expression, whereas TSA had a mild effect. Further research involving larger cohorts is needed to confirm these findings.

Melanoma, a globally prevalent skin cancer with over 325,000 new cases annually, necessitates a comprehensive under- standing of its molecular components. This study looks at the PRAME (cutaneous melanoma-associated antigen) and BAP1 (gene controlling gene-environment interactions) proteins. Both PRAME and BAP1 are associated with critical genomic alterations that significantly influence melanoma progression and patient outcomes. PRAME is overexpressed in various cancers, especially uveal melanoma (UM), where high levels correlate with poor prognosis and genomic instability linked to chromosome 8q12 alterations. Meanwhile, mutations in BAP1 contribute to increased genomic instability and a higher risk of metastasis in UM, highlighting its importance as a key prognostic marker in tumorigenesis. Established approaches along with features proposed in this work are used to investigate sequence conservation, polyglutamic acid presence, intrinsic disorder of proteins, polar-nonpolar residues arrangement PRAME and BAP1 conserved residues highlight their critical roles in protein function and interaction. Sequence invariance indicates the possibility of functional relevance and evolutionary conservation. PRAME has enhanced intrinsic disorder and flexibility, whereas BAP1 has changed disorder-promoting residue sequences. Polyglutamic acid strings are found in both proteins, emphasizing their modulatory involvement in protein interactions. The ratios and spatial arrangement of amino acids have a profound influence on interactions and gene dysregulation. This work contributes to a better knowledge of the two melanoma-associated proteins viz. PRAME and BAP1 by unraveling their structural and functional complexities.

Melanoma-associated antigen (MAGE)-A4, a cancer testis antigen, presents a promising target for chimeric antigen receptor T cell therapy in refractory solid tumors, including breast cancer (BC). However, the lack of highly specific Abs against MAGE-A4 is a major challenge for the development of MAGE-A4-targeted immunotherapies. This study aimed to validate the specificity of a novel MAGE-A4 Ab (E701U) and examine MAGE-A4 expression in clinical BC samples. MAGE-A1, -A2B, -A3, -A4, -A6, -A9, -A10, and -A12 genes were transfected into HEK293 cells. MAGE-A4 expression in each inserted cell block was evaluated using an E701U Ab. Subsequently, we evaluated MAGE-A4 expression in 403 primary BC tissue samples by immunohistochemistry using E701U and analyzed the clinical impact of MAGE-A4 in patients with early BC. The results showed that MAGE-A4 expression was limited to cells transduced with the MAGE-A4 gene. MAGE-A4 expression was observed in 5.7% of the BC samples. Positivity in triple-negative BC was significantly higher than in the other subtypes. The 5-year overall survival rate of patients with MAGE-A4(+) was significantly worse than those with MAGE-A4(-) BC. Moreover, the 5-year recurrence-free survival (RFS) rate of patients with MAGE-A4(+) BC was significantly lower than that of patients with MAGE-A4(-) BC. MAGE-A4 expression was an independent prognostic factor for RFS. In conclusion, the E701U Ab showed reliable specificity for MAGE-A4 expression among MAGE family genes. Patients with MAGE-A4(+) BC have an unfavorable prognosis and represent potential candidates for MAGE-A4-specific immunotherapy.

T-cell receptor (TCR) T-cell therapies are adoptive cell therapies in which patient cells are engineered to express TCRs targeting specific cancer antigens and infused back into the patient. Since TCR recognition depends on antigen presentation by the human leukocyte antigen system, TCRs can respond to intracellular antigens. Cancer/testis antigens (CTAs) are a large family of proteins, many of which are only expressed in cancerous tissue and immune-privileged germline sites. Melanoma-associated antigen A4 (MAGE-A4) is an intracellular CTA expressed in healthy testis and placenta, and in a range of cancers, including esophageal, head and neck, gastric, ovarian, colorectal, lung, endometrial, cervical, bladder, breast and prostate cancers; soft tissue sarcomas; urothelial and hepatocellular carcinomas; osteosarcoma; and melanoma. This expression pattern, along with the immunogenicity and potential role in tumorigenesis of MAGE-A4 make it a prime target for TCR T-cell therapy. We outline the preclinical and clinical development of TCR T-cell therapies targeting CTAs for treatment of solid tumors, highlighting the need for extensive preclinical characterization of putative off-target, and potential on-target but off-tumor, effects. We identified ten clinical trials assessing TCR T-cell therapies targeting MAGE-A4. Overall, manageable safety profiles and signals of efficacy have been observed, especially in patients with advanced synovial sarcoma, myxoid/round cell liposarcoma, ovarian, head and neck, and urothelial cancers, with one TCR T-cell therapy approved by the US Food and Drug Administration in August 2024. We also review the limitations, and strategies to enhance efficacy and improve safety, of these therapies, and summarize related immunotherapies targeting MAGE-A4.

Tumour-associated microbiota are integral components of the tumour microenvironment (TME). However, previous studies on intratumoral microbiota primarily rely on bulk tissue analysis, which may obscure their spatial distribution and localized effects. In this study, we applied in situ spatial-profiling technology to investigate the spatial distribution of intratumoral microbiota in breast cancer and their interactions with the local TME. Using 5R 16S rRNA gene sequencing and RNAscope FISH/CISH on patients' tissue, we identified significant spatial heterogeneity in intratumoral microbiota, with Fusobacterium nucleatum (F. nucleatum) predominantly localized in tumour cell-rich areas. GeoMx digital spatial profiling (DSP) revealed that regions colonized by F. nucleatum exhibit significant influence on the expression of RNAs and proteins involved in proliferation, migration and invasion. In vitro studies indicated that co-culture with F. nucleatum significantly stimulates the proliferation and migration of breast cancer cells. Integrative spatial multi-omics and co-culture transcriptomic analyses highlighted the MAPK signalling pathways as key altered pathways. By intersecting these datasets, VEGFD and PAK1 emerged as critical upregulated proteins in F. nucleatum-positive regions, showing strong positive correlations with MAPK pathway proteins. Moreover, the upregulation of VEGFD and PAK1 by F. nucleatum was confirmed in co-culture experiments, and their knockdown significantly reduced F. nucleatum-induced proliferation and migration. In conclusion, intratumoral microbiota in breast cancer exhibit significant spatial heterogeneity, with F. nucleatum colonization markedly altering tumour cell protein expression to promote progression and migration. These findings provide novel perspectives on the role of microbiota in breast cancer, identify potential therapeutic targets, and lay the foundation for future cancer treatments. KEY POINTS: Intratumoral Fusobacterium nucleatum exhibits significant spatial heterogeneity within breast cancer tissues. F. nucleatum colonization alters the expression of key proteins involved in tumour progression and migration. The MAPK signalling pathway is a critical mediator of F. nucleatum-induced breast cancer cell proliferation and migration. VEGFD and PAK1 are potential therapeutic targets to mitigate F. nucleatum-induced tumour progression.

The Cancer Testis Antigens (CTAs) are a group of germ cell proteins that are absent from normal somatic cells yet aberrantly expressed in many cancer cells. When mis-expressed in cancer cells, many CTAs promote tumorigenic characteristics including genome instability, DNA damage tolerance and therapy resistance. Here we highlight some of the CTAs for which their roles in genome maintenance in cancer cells are well established. We consider three broad CTA categories: (1) Melanoma Antigens (MAGEs) (2) Mitotic CTAs and (3) CTAs with roles in meiotic homologous recombination. Many cancer cells rely on CTAs to tolerate intrinsic and therapy-induced genotoxic stress. Therefore, CTAs represent molecular vulnerabilities of cancer cells and may provide opportunities for therapy. Owing to their high-level expression in tumors and absence from normal somatic cells, CTA-directed therapies could have a high level of specificity and would likely be devoid of side-effect toxicity.

Cancer vaccines, aimed at evolving the human immune system to eliminate tumor cells, have long been explored as a method of cancer treatment with significant clinical potential. Traditional delivery systems face significant challenges in directly targeting tumor cells and delivering adequate amounts of antigen due to the hostile tumor microenvironment. Emerging evidence suggests that certain bacteria naturally home in on tumors and modulate antitumor immunity, making bacterial vectors a promising vehicle for precision cancer vaccines. Live bacterial vehicles offer several advantages, including tumor colonization, precise drug delivery, and immune stimulation, making them a compelling option for cancer immunotherapy. In this review, we explore the mechanisms of action behind living bacteria-based vaccines, recent progress in popular bacterial chassis, and strategies for specific payload delivery and biocontainment to ensure safety. These approaches will lay the foundation for developing an affordable, widely applicable cancer vaccine delivery system. This review also discusses the challenges and future opportunities in harnessing bacterial-based vaccines for enhanced therapeutic outcomes in cancer treatment.

Over the years, extensive research has been dedicated to performing in-depth analysis of cancer to uncover the intricate details of its nature - including the types of cancer, causative agents, stimulators of disease progression, factors contributing to poor prognosis, and efficient therapies to restrict the metastatic aggressiveness. This chapter highlights the mechanisms through which different arms of the host immune system - namely cytokines, lymphocytes, antigen-presenting cells (APCs) -can be mobilized to eradicate cancer. Most malignant tumors are either poorly immunogenic, or are harbored in a highly immuno-suppressive microenvironment. This is why reinforcing the host's anti-tumor defenses, through infusion of pro-inflammatory cytokines, tumor antigen-loaded APCs, and anti-tumor cytotoxic cells has emerged as a viable treatment option against cancer. The chapter also highlights the ongoing preclinical and clinical studies in different malignancies and the outcome of various therapies. Although these methods are not foolproof, and antigen escape variants can still evade or develop resistance to customized therapies, they achieve disease stabilization in several cases when conventional treatments fail. In many instances, combination therapies involving cytokines, T cells, and vaccinations prove more effective than monotherapies. The limitations of the current therapies are also discussed, along with ongoing modifications aimed at improving efficacy.

Medulloblastoma is the most frequent malignant primary brain tumor in children. Despite recent advances in integrated genomics, the prognosis in children with high-risk medulloblastoma remains devastating, and new tumor-specific therapeutic approaches are needed. Here, we present an atlas of naturally presented T cell antigens in medulloblastoma. We map the human leukocyte antigen (HLA)-presented peptidomes of 28 tumors and perform comparative immunopeptidome profiling against an in-house benign database. Medulloblastoma is shown to be a rich source of tumor-associated antigens, naturally presented on HLA class I and II molecules. Remarkably, most tumor-associated peptides and proteins are subgroup-specific, whereas shared presentation among all subgroups of medulloblastoma (WNT, SHH, Group 3 and Group 4) is rare. Functional testing of top-ranking novel candidate antigens demonstrates the induction of peptide-specific T cell responses, supporting their potential for T cell immunotherapy. This study is an in-depth mapping of naturally presented T cell antigens in medulloblastoma. Integration of immunopeptidomics, transcriptomics, and epigenetic data leads to the identification of a large set of actionable targets that can be further used for the translation into the clinical setting by facilitating the informed design of immunotherapeutic approaches to children with medulloblastoma.

MAGE A4 (Melanoma Antigen Gene A4) is a cancer testis antigen (CTA) that is expressed normally in germline cells (testis/embryonic tissues) but absent in somatic cells. The MAGE A4 CTA is expressed in a variety of tumor types, like synovial sarcoma, ovarian cancer and non-small cell lung cancer. Having its expression profile limited to germline cells has made MAGE A4 a sought-after immunotherapeutic target in certain malignancies. In this review, we focus on MAGE-A4's function and expression, current clinical trials involving targeted immunotherapy approaches, and challenges and opportunities facing MAGE-A4's targeted therapeutics.

The application of messenger RNA (mRNA) technology in antigen-based immuno-oncology therapies represents a significant advancement in cancer treatment. Cancer vaccines are an effective combinatorial partner to sensitize the host immune system to the tumor and boost the efficacy of immune therapies. Selecting suitable tumor antigens is the key step to devising effective vaccinations and amplifying the immune response. Tumor neoantigens are de novo epitopes derived from somatic mutations, avoiding T-cell central tolerance of self-epitopes and inducing immune responses to tumors. The identification and prioritization of patient-specific tumor neoantigens are based on advanced computational algorithms taking advantage of the profiling with next-generation sequencing considering factors involved in human leukocyte antigen (HLA)-peptide-T-cell receptor (TCR) complex formation, including peptide presentation, HLA-peptide affinity, and TCR recognition. This review discusses the development and clinical application of mRNA vaccines in oncology, with a particular focus on recent clinical trials and the computational workflows and methodologies for identifying both shared and individual antigens. While this review centers on therapeutic mRNA vaccines targeting existing tumors, it does not cover preventative vaccines. Preclinical experimental validations are crucial in cancer vaccine development, but we emphasize the computational approaches that facilitate neoantigen selection and design, highlighting their role in advancing mRNA vaccine development. The versatility and rapid development potential of mRNA make it an ideal platform for personalized neoantigen immunotherapy. We explore various strategies for antigen target identification, including tumor-associated and tumor-specific antigens and the computational tools used to predict epitopes capable of eliciting strong immune responses. We address key design considerations for enhancing the immunogenicity and stability of mRNA vaccines, as well as emerging trends and challenges in the field. This comprehensive overview highlights the therapeutic potential of mRNA-based cancer vaccines and underscores ongoing research efforts aimed at optimizing these therapies for improved clinical outcomes.

The field of cancer immunotherapy has experienced remarkable advancements in the treatment of human cancers over recent decades. Therapeutic cancer vaccines have been employed to elicit antitumor immune responses through the generation of specific reactions against tumor-associated antigens. Although preclinical studies have demonstrated hopeful results and at least one product is approved for clinical use, the overall efficacy of cancer vaccines remains restricted. The co-administration of anti-checkpoint antibodies alongside cancer vaccines is proposed as a potential strategy to enhance the clinical efficacy of immunotherapies. Among the various anti-checkpoint agents, monoclonal antibodies targeting CD127, OX40, and CD40 have been further investigated in combined administration with cancer vaccines, demonstrating a synergistic impact on disease outcomes in both animal models and human subjects. This combinational approach has been shown to suppress tumor regression, improve survival rates, and promote the efficacy of cancer vaccines via multiple mechanisms, including the augmentation of generation, activation, and expansion of CD8+ T cells, as well as the production of tumor-inhibitory cytokines. Importantly, the impact of the concurrent administration of anti-checkpoint agents and cancer vaccines surpass those observed with the sole vaccine, indicating that this strategy may offer significant advantages for clinical application in cancer patients. In this review, we aim to provide a comprehensive overview of the significance and therapeutic potential of the combined administration of checkpoint agonist/antagonist antibodies and cancer vaccines for human tumors.

Effective anti-tumor immunity is driven by cytotoxic CD8+ T cells with specificity for tumor antigens. However, the factors that control successful tumor rejection are not well understood. Here we identify a subpopulation of CD8+ T cells that are tumor-antigen-specific and can be identified by KIR expression but paradoxically impair anti-tumor immunity in patients with melanoma. These tumor-antigen-specific KIR+CD8+ regulatory T cells target other tumor-antigen-specific CD8+ T cells, can be detected in both the tumor and the blood, have a conserved transcriptional program and are associated with a poor overall survival. These findings broaden our understanding of the transcriptional and functional heterogeneity of human CD8+ T cells and implicate KIR+CD8+ regulatory T cells as a cellular mediator of immune evasion in human cancer.

MicroRNAs (miRNAs) are crucial factors in gene regulation, and their dysregulation plays important roles in the immunity of gastric cancer (GC). However, finding specific and effective miRNA markers is still a great challenge for GC immunotherapy. In this study, we computed and analysed miRNA-seq, RNA-seq and clinical data of GC patients from the TCGA database. With the comparison of tumour and normal tissues in GC, we identified 2056 upregulated and 2311 downregulated protein-coding genes. Based on the miRNet database, more than 2600 miRNAs interact with these genes. Several key miRNAs, including hsa-mir-34a, hsa-mir-182 and hsa-mir-23b, were identified to potentially play important regulatory roles in the expression of most upregulated and downregulated genes in GC. Based on bioinformation approaches, the expressions of hsa-mir-34a and hsa-mir-182 were closely linked to the tumour stage, and high expression of hsa-mir-23b was correlated with poor survival in GC. Moreover, these three miRNAs are involved in immune cell infiltration (such as activated memory CD4 T cells and resting mast cells), particularly hsa-mir-182 and hsa-mir-23b. GSEA suggested that the changes in their expression may possibly activate/inhibit immune-related signal pathways, such as chemokine signalling pathway and CXCR4 pathway. These results will provide possible miRNA markers or targets for combined immunotherapy of GC.

This mini-review explores recent advancements in cancer vaccines that target Wilms' tumor (WT1). Phase I/II trials of WT1 peptide vaccines have demonstrated their safety and efficacy against various cancers. Early trials employing HLA class I peptides evolved through their combination with HLA class II peptides, resulting in improved clinical outcomes. Additionally, WT1-targeted dendritic cell vaccines have exhibited favorable results. Studies focusing on hematological malignancies have revealed promising outcomes, including long-term remission and extended survival times. The combination of vaccines with immune checkpoint inhibitors has shown synergistic effects. Current preclinical developments are focused on enhancing the effectiveness of WT1 vaccines, underscoring the necessity for future large-scale Phase III trials to further elucidate their efficacy.

The research and development of messenger RNA (mRNA) cancer vaccines have gradually overcome numerous challenges through the application of personalized cancer antigens, structural optimization of mRNA, and the development of alternative RNA-based vectors and efficient targeted delivery vectors. Clinical trials are currently underway for various cancer vaccines that encode tumor-associated antigens (TAAs), tumor-specific antigens (TSAs), or immunomodulators. In this paper, we summarize the optimization of mRNA and the emergence of RNA-based expression vectors in cancer vaccines. We begin by reviewing the advancement and utilization of state-of-the-art targeted lipid nanoparticles (LNPs), followed by presenting the primary classifications and clinical applications of mRNA cancer vaccines. Collectively, mRNA vaccines are emerging as a central focus in cancer immunotherapy, offering the potential to address multiple challenges in cancer treatment, either as standalone therapies or in combination with current cancer treatments.

An 11-year-old spayed female Beagle presented with tenesmus and was identified with a rectal wall mass. Diagnostic imaging (abdominal ultrasound and computed tomography) localised the mass in the right rectal wall and documented no evidence of metastatic disease. Subsequently, the dog underwent surgery for tumour excision. A histopathological diagnosis of melanoma was performed. To confirm the tumour histotype, immunohistochemistry was performed using anti-Melan A and anti-Ki67. Neoplastic cells exhibited focal Melan A immunoreactivity and widespread nuclear immunoreactivity for Ki67 with a Ki67 index of 27%. Adjuvant immunotherapy with APAVAC® was initiated. After APAVAC administration, no local or systemic acute adverse events were observed. Four pre- and post-contrast computed tomography (CT) studies were performed in an 18-month follow-up period every 4-5 months. Follow-up rectal palpation and conscious visualisation of the surgical site have also resulted in no macroscopic signs of tumour recurrence. The dog remains alive and with no clinical evidence of tumour recurrence and/or distant progression at the time of writing, therefore, surviving over 540 days from the diagnosis.

Cancer has agonized the human race for millions of years. The present decade witnesses biological therapeutics to combat cancer effectively. Cancer Immunotherapy involves the use of therapeutics for manipulation of the immune system by immune agents like cytokines, vaccines, and transfection agents. Recently, this therapeutic approach has got vast attention due to the current pandemic COVID-19 and has been very effective. Concerning cancer, immunotherapy is based on the activation of the host's antitumor response by enhancing effector cell number and the production of soluble mediators, thereby reducing the host's suppressor mechanisms by induction of a tumour killing environment and by modulating immune checkpoints. In the present era, immunotherapies have gained traction and momentum as a pedestal of cancer treatment, improving the prognosis of many patients with a wide variety of haematological and solid malignancies. Food supplements, natural immunomodulatory drugs, and phytochemicals, with recent developments, have shown positive trends in cancer treatment by improving the immune system. The current review presents the systematic studies on major immunotherapeutics and their development for the effective treatment of cancers as well as in COVID-19. The focus of the review is to highlight comparative analytics of existing and novel immunotherapies in cancers, concerning immunomodulatory drugs and natural immunosuppressants, including immunotherapy in COVID-19 patients.

Cancer is a complex, multistep process characterized by abnormal cell growth and metastasis as well as the capacity of the tumor cells in therapy resistance development. The urological system is particularly susceptible to a group of malignancies known as urological cancers, where an accumulation of genetic alterations drives carcinogenesis. In various human cancers, Wnt singalling is dysregulated; following nuclear transfer of β-catenin, it promotes tumor progression and affects genes expression. Elevated levels of Wnt have been documented in urological cancers, where its overexpression enhances growth and metastasis. Additionally, increased Wnt singalling contributes to chemoresistance in urological cancers, leading to reduced sensitivity to chemotherapy agents like cisplatin, doxorubicin, and paclitaxel. Wnt upregulation can change radiotherapy response of urological cancers. The regulation of Wnt involves various molecular pathways, including Akt, miRNAs, lncRNAs, and circRNAs, all of which play roles in carcinogenesis. Targeting and silencing Wnt or its associated pathways can mitigate tumorigenesis in urological cancers. Anti-cancer compounds such as curcumin and thymoquinone have shown efficacy in suppressing tumorigenesis through the downregulation of Wnt singalling. Notably, nanoparticles have proven effective in treating urological cancers, with several studies in prostate cancer (PCa) using nanoparticles to downregulate Wnt and suppress tumor growth. Future research should focus on developing small molecules that inhibit Wnt singalling to further suppress tumorigenesis and advance the treatment of urological cancers. Moreover, Wnt can be used as reliable biomarker for the diagnosis and prognosis of urological cancers.

Cancer immunobiology is one of the hot topics of discussion amongst researchers today, and immunotherapeutic modalities are among the selected few emerging approaches to cancer treatment that have exhibited a promising outlook. However, immunotherapy is not a new kid on the block; it has been around for centuries. The origin of cancer immunotherapy in modern medicine can be traced back to the initial reports of spontaneous regression of malignant tumors in some patients following an acute febrile infection, at the turn of the twentieth century. This review briefly revisits the historical accounts of immunotherapy, highlighting some of the significant developments in the field of cancer immunobiology, that have been instrumental in bringing back the immunotherapeutic approaches to the forefront of cancer research. Some of the topics covered are: Coley's toxin-the first immunotherapeutic; the genesis of the theory of immune surveillance; the discovery of T lymphocytes and dendritic cells and their roles; the role of tumor antigens; relevance of tumor microenvironment; the anti-tumor (therapeutic) ability of Bacillus Calmette- Guérin; Melacine-the first therapeutic vaccine engineered; theories of immunoediting and immunophenotyping of cancer; and Provenge-the first FDA-approved therapeutic vaccine. In this review, head and neck cancer has been taken as the reference tumor for narrating the progression of cancer immunobiology, particularly for highlighting the advent of immunotherapeutic agents.

Immunotherapy offers a novel and promising option in the treatment of late-stage melanoma. By utilizing the immune system to assist in tumor destruction, patients have additional options after tumor progression. Immune checkpoint inhibitors reduce the ability for tumors to evade the immune system by inhibiting key surface proteins used to inactivate T-cells. Without these surface proteins, T-cells can induce cytotoxic responses against tumors. Tumor infiltrating lymphocyte therapy is a form of adoptive cell therapy that takes advantage of a small subset of T-cells that recognize and infiltrate tumors. Isolation and rapid expansion of these colonies assist the immune system in mounting a charged response that can induce remission. Tumor vaccines deliver a high dose of unique antigens expressed by tumor cells to the entire body. The introduction of large quantities of tumor antigens upregulates antigen presenting cells and leads to effective activation of the immune system against tumors. Cytokine therapy introduces high amounts of chemical messengers that are endogenous to the immune system and support T-cell expansion. While other methods of immunotherapy exist, immune checkpoint inhibitors, tumor infiltrating lymphocytes, tumor vaccines, and cytokine therapy are commonly used to treat melanoma. Like many other cancer treatments, immunotherapy is not without adverse effects, as toxicities represent a major obstacle. However, immunotherapy has been efficacious in the treatment of melanoma.

Over the past few decades, research on cancer immunotherapy has firmly established immune cells as key players in effective cancer treatment. Peptide vaccines directly targeting immune cells have demonstrated immense potential due to their specificity and applicability. However, developing peptide vaccines to generate tumor-reactive T cells remains challenging, primarily due to suboptimal immunogenicity and overcoming the immunosuppressive tumor microenvironment (TME). In this review, we discuss various elements of effective peptide vaccines, including antigen selection, peptide epitope optimization, vaccine adjuvants, and the combination of multiple immunotherapies, in addition to recent advances in tumor neoantigens as well as epitopes bound by non-classical human leukocyte antigen (HLA) molecules, to increase the understanding of cancer peptide vaccines and provide multiple references for the design of subsequent T cell-based peptide vaccines.

Recent advances in tumor immunology and molecular drug development have ushered in a new era of cancer immunotherapy. Immunotherapy has shown promising results for several types of tumors, such as advanced melanoma, non-small cell lung cancer, renal cell carcinoma, bladder cancers, and refractory Hodgkin's lymphoma. Similarly, efforts have been made to develop immunotherapies such as adoptive T-cell transplantation, peptide vaccines, and dendritic cell vaccines, specifically for gastrointestinal tumors. However, before the advent of immune checkpoint inhibitors, immunotherapy did not work as well as expected. In this article, we review immunotherapy, focusing on cancer vaccines for gastrointestinal tumors, which generally target eliciting tumor-specific CD8 + cytotoxic T lymphocytes (CTLs). We also review various vaccine therapies and describe the relationship between vaccines and adjuvants. Finally, we discuss prospects for the combination of immunotherapy with immune checkpoint inhibitors.

Metastasis, the dissemination of malignant cells from a primary tumor to secondary sites, poses a catastrophic burden to cancer treatment and is the predominant cause of mortality in cancer patients. Metastasis as one of the main aspects of cancer progression could be strongly under the influence of viral infections. In fact, viruses have been central to modern cancer research and are associated with a great number of cancer cases. Viral-encoded elements are involved in modulating essential pathways or specific targets that are implicated in different stages of metastasis. Considering the continuous emergence of new viruses and the establishment of their contribution to cancer progression, the warfare between viruses and cancer appears to be endless. Here we aimed to review the critical mechanism and pathways involved in cancer metastasis and the influence of viral machinery and various routes that viruses adopt to manipulate those pathways for their benefit.

Glioma has a poor prognosis, which is attributable to its inherent characteristics and lack of specific treatments. Immunotherapy plays a pivotal role in the contemporary management of malignancies. Despite the initiation of numerous immunotherapy-based clinical trials, their effects on enhancing glioma prognosis remain limited, highlighting the need for innovative and effective therapeutic targets and strategies to address this challenge. Since the 1990s, there has been a growing interest in cancer-testis antigens (CTAs) present in normal mammalian testicular germ cells and placental trophoblast cells, which exhibit reactivated expression in various tumor types. Mechanisms such as DNA methylation, histone modification, transcriptional regulation, and alternative splicing influence the expression of CTAs in tumors. The distinct expression patterns and robust immunogenicity of CTAs are promising tumor biomarkers and optimal targets for immunotherapy. Previous reports have shown that multiple CTAs are present in gliomas and are closely related to prognosis. The expression of these antigens is also associated with the immune response in gliomas and the effectiveness of immunotherapy. Significantly, numerous clinical trials, with IL13RA2 as a representative CTA member, have assessed the immunotherapeutic potential of gliomas and have shown favorable clinical efficacy. This review provides a comprehensive overview of the regulation and function of CTAs, summarizes their expression and role in gliomas, emphasizes their importance as immunotherapy targets in gliomas, and discusses related challenges and future interventions.

Recent breakthroughs in cancer immunotherapies have emphasized the importance of harnessing the immune system for treating cancer. Vaccines, which have traditionally been used to promote protective immunity against pathogens, are now being explored as a method to target cancer neoantigens. Over the past few years, extensive preclinical research and more than a hundred clinical trials have been dedicated to investigating various approaches to neoantigen discovery and vaccine formulations, encouraging development of personalized medicine. Nucleic acids (DNA and mRNA) have become particularly promising platform for the development of these cancer immunotherapies. This shift towards nucleic acid-based personalized vaccines has been facilitated by advancements in molecular techniques for identifying neoantigens, antigen prediction methodologies, and the development of new vaccine platforms. Generating these personalized vaccines involves a comprehensive pipeline that includes sequencing of patient tumor samples, data analysis for antigen prediction, and tailored vaccine manufacturing. In this review, we will discuss the various shared and personalized antigens used for cancer vaccine development and introduce strategies for identifying neoantigens through the characterization of gene mutation, transcription, translation and post translational modifications associated with oncogenesis. In addition, we will focus on the most up-to-date nucleic acid vaccine platforms, discuss the limitations of cancer vaccines as well as provide potential solutions, and raise key clinical and technical considerations in vaccine development.

T lymphocytes are indispensable for the host systems of defense against pathogens, tumors, and environmental threats. The therapeutic potential of harnessing the cytotoxic properties of T lymphocytes for antigen-specific cell elimination is both evident and efficacious. Genetically engineered T-cells, such as those employed in CAR-T and TCR-T cell therapies, have demonstrated significant clinical benefits in treating cancer and autoimmune disorders. However, the current landscape of T-cell genetic engineering is dominated by strategies that necessitate in vitro T-cell isolation and modification, which introduce complexity and prolong the development timeline of T-cell based immunotherapies. This review explores the complexities of gene delivery systems designed for T cells, covering both viral and nonviral vectors. Viral vectors are known for their high transduction efficiency, yet they face significant limitations, such as potential immunogenicity and the complexities involved in large-scale production. Nonviral vectors, conversely, offer a safer profile and the potential for scalable manufacturing, yet they often struggle with lower transduction efficiency. The pursuit of gene delivery systems that can achieve targeted gene transfer to T cell without the need for isolation represents a significant advancement in the field. This review assesses the design principles and current research progress of such systems, highlighting the potential for in vivo gene modification therapies that could revolutionize T-cell based treatments. By providing a comprehensive analysis of these systems, we aim to contribute valuable insights into the future development of T-cell immunotherapy.

Mature erythrocytes are known to lack major histocompatibility complex (MHC) proteins. However, the presence of MHC molecules on erythrocytes has been occasionally reported, though without a defined function. In this study, we designed erythrocyte conjugated solely with a fusion protein consisting of an antigenic peptide linked to MHC class I (MHC-I) protein, termed MHC-I‒Ery. The modified erythrocyte, decorated with the peptide derived from human papillomavirus (HPV) 16 oncoprotein E6/E7, effectively activated antigen-specific CD8+ T cells in peripheral blood mononuclear cells (PBMCs) from HPV16+ cervical cancer patients. Additionally, MHC-I‒Ery monotherapy was shown to inhibit antigen-positive tumor growth in mice. This treatment immediately activated CD8+ T cells and reduced suppressive myeloid cells in the spleen, leading to systemic anti-tumor activity. Safety and tolerability evaluations of MHC-I‒Ery in non-human primates further supported its clinical potential. Our results first demonstrated that erythrocytes equipped solely with antigen peptide‒MHC-I complexes can robustly stimulate the immune system, suggesting a novel and promising approach for advancing cancer immunotherapy.

Vaccinations are essential for preventing and treating disease, especially cancer nanovaccines, which have gained considerable interest recently for their strong anti-tumor immune capabilities. Vaccines can prompt the immune system to generate antibodies and activate various immune cells, leading to a response against tumor tissues and reducing the negative effects and recurrence risks of traditional chemotherapy and surgery. To enhance the flexibility and targeting of vaccines, nanovaccines utilize nanotechnology to encapsulate or carry antigens at the nanoscale level, enabling more controlled and precise drug delivery to enhance immune responses. Cancer nanovaccines function by encapsulating tumor-specific antigens or tumor-associated antigens within nanomaterials. The small size of these nanomaterials allows for precise targeting of T cells, dendritic cells, or cancer cells, thereby eliciting a more potent anti-tumor response. In this paper, we focus on the classification of carriers for cancer nanovaccines, the roles of different target cells, and clinically tested cancer nanovaccines, discussing strategies for effectively inducing cytotoxic T lymphocytes responses and optimizing antigen presentation, while also looking ahead to the translational challenges of moving from animal experiments to clinical trials.

The incidence of lung cancer continues to grow globally, contributing to an ever-increasing load on healthcare systems. Emerging evidence has indicated lowered efficacy of conventional treatment strategies, such as chemotherapy, surgical interventions and radiotherapy, prompting the need for exploring alternative interventions. A growing focus on immunotherapy and the development of personalized medicine has paved the way for vaccine-based delivery in lung cancer. With various prominent targets such as CD8+T cells and PD-L1, immune-targeted, anti-cancer vaccines have been evaluated in both, pre-clinical and clinical settings, to improve therapeutic outcomes. However, there are a number of challenges that must be addressed, including the scalability of such delivery systems, heterogeneity of lung cancers, and long-term safety as well as efficacy. In addition to this, natural compounds, in combination with immunotherapy, have gained considerable research interest in recent times. This makes it necessary to explore their role in synergism with immune-targeted agents. The authors of this review aim to offer an overview of recent advances in our understanding of lung cancer pathogenesis, detection and management strategies, and the emergence of immunotherapy with a special focus on vaccine delivery. This finding is supported with evidence from testing in non-human and human models, showcasing promising results. Prospects for phytotherapy have also been discussed, in order to combat some pitfalls and limitations. Finally, the future perspectives of vaccine usage in lung cancer management have also been discussed, to offer a holistic perspective to readers, and to prompt further research in the domain.

Characterization of T-cell receptors (TCRs) repertoire was revolutionized by next-generation sequencing technologies; however, standardization using biological controls to facilitate precision of current alignment and assembly tools remains a challenge. Additionally, availability of TCR libraries for off-the-shelf cloning and engineering TCR-specific T cells is a valuable resource for TCR-based immunotherapies. We established nine human TCR α and β clones that were evaluated using the 5'-rapid amplification of cDNA ends-like RNA-based TCR sequencing on the Illumina platform. TCR sequences were extracted and aligned using MiXCR, TRUST4, and CATT to validate their sensitivity and specificity and to validate library preparation methods. The correlation between actual and expected TCR ratios within libraries confirmed accuracy of the approach. Our findings established the development of biological standards and library of TCR clones to be leveraged in TCR sequencing and engineering. The remaining human TCR clones' libraries for a more diverse biological control will be generated.