Neoantigen-based immunotherapy has emerged as a transformative approach in cancer treatment, offering precision medicine strategies that target tumor-specific antigens derived from genetic, transcriptomic, and proteomic alterations unique to cancer cells. These neoantigens serve as highly specific targets for personalized therapies, promising more effective and tailored treatments. The aim of this article is to explore the advances in neoantigen-based therapies, highlighting successful treatments such as vaccines, tumor-infiltrating lymphocyte (TIL) therapy, T-cell receptor-engineered T cells therapy (TCR-T), and chimeric antigen receptor T cells therapy (CAR-T), particularly in cancer types like glioblastoma (GBM). Advances in technologies such as next-generation sequencing, RNA-based platforms, and CRISPR gene editing have accelerated the identification and validation of neoantigens, moving them closer to clinical application. Despite promising results, challenges such as tumor heterogeneity, immune evasion, and resistance mechanisms persist. The integration of AI-driven tools and multi-omic data has refined neoantigen discovery, while combination therapies are being developed to address issues like immune suppression and scalability. Additionally, the article discusses the ongoing development of personalized immunotherapies targeting tumor mutations, emphasizing the need for continued collaboration between computational and experimental approaches. Ultimately, the integration of cutting-edge technologies in neoantigen research holds the potential to revolutionize cancer care, offering hope for more effective and targeted treatments.

Emerging cancer immunotherapy methods, notably cytokine-based ones that modify immune systems’ inflammatory reactions to tumor cells, may help slow gastric cancer progression. Cytokines, tiny signaling proteins that communicate between immune cells, may help or hinder cancer growth. Pro-inflammatory cytokines encourage tumor development, whereas antitumor ones help the host reject cancer cells. This study considers cytokine-targeted methods for gastric cancer pro-inflammatory and antitumor immune responses. Researchers want to renew immune cells like cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells by delivering cytokines like interleukin-2 (IL-2), interferons (IFNs), and tumor necrosis factor-alpha (TNF-α) to activate inflammatory pathways and combat tumors. Since cytokines have significant pleiotropic effects, their therapeutic use is difficult and may cause excessive systemic inflammation or immunological suppression. This review covers current advancements in synthetic cytokines, cytokine-conjugates, and local administration of these aimed to enhance the therapeutic index: increase the potential to kill cancer cells while minimizing off-target damage. The study examines the relationship between cytokines and tumor microenvironment (TME), revealing the role of immunosuppressive cytokines like IL-10 and transforming growth factor-beta (TGF-β) in promoting an immune-evasive phenotype. These results suggest that inhibitory pathway targeting, and cytokine-based therapy may overcome resistance mechanisms. Cytokine-based immunotherapies combined with immune checkpoint inhibitors are predicted to change gastric cancer therapy and rebuild tumor-immune microenvironment dynamics, restoring antitumor immunity. Comprehensive data from current clinical studies will assist in establishing the position of these treatments in gastric cancer.

This review explores the intricate relationship between viral infections and Bacillus Calmette-Guerin (BCG) efficacy, emphasizing immune modulation mechanisms that may influence treatment outcomes. Since its introduction in 1976, intravesical BCG has been a cornerstone in managing non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumors (TURBT). Despite its success, variability in response rates suggests that host immune status, influenced by persistent infections, immunosenescence, and antigenic overload, may play a crucial role in therapeutic effectiveness. Chronic viral infections can modulate T cell responses, leading to immune exhaustion and impaired antitumor immunity. This review discusses the interplay between viral antigenic load, immune dysfunction, and tumor microenvironment remodeling, highlighting their potential impact on immunotherapies. By integrating insights from virome analysis, immune profiling, and tumor characterization, this review proposes personalized strategies to enhance immunotherapy efficacy. A deeper understanding of viral-induced immune dysregulation may improve prognostic assessment, optimize treatment protocols, and reduce healthcare costs associated with bladder cancer. Future research should focus on targeted interventions to mitigate the immunosuppressive effects of chronic infections, ultimately improving patient outcomes in NMIBC management.

Exportin-1 (XPO1) is a nuclear export protein that, when overexpressed, can facilitate cancer cell proliferation and survival and is frequently overexpressed or mutated in cancer patients. As such, selective inhibitors of XPO1 (XPO1i) function have been developed to inhibit cancer cell proliferation and induce apoptosis. This review outlines the evidence for the immunomodulatory properties of XPO1 inhibition and discusses the potential for combining and sequencing XPO1i with immunotherapy to improve the treatment of patients with cancer. Selinexor is a first-in-class XPO1i that is FDA-approved for the treatment of patients with relapsed and refractory (RR) multiple myeloma and RR diffuse large B cell lymphoma. In addition to the cancer cell intrinsic pro-apoptotic activity, increasing evidence suggests that XPO1 inhibition has immunomodulatory properties. In this review, we describe how XPO1i can lead to a skewing of macrophage polarisation, inhibition of neutrophil extracellular traps, modulation of immune checkpoint expression, blockade of myeloid-derived suppressor cells (MDSCs) and sensitisation of cancer cells to T cell and NK (natural killer) cell immunosurveillance. As such, there is an opportunity for selinexor to enhance immunotherapy efficacy and thus a need for clinical trials assessing selinexor in combination with immunotherapies such as immune checkpoint inhibitors, direct targeting monoclonal antibodies, chimeric antigen receptor (CAR)-T cells and cereblon E3 ligase modulators (CELMoDs).

The ultrastructural morphology of eosinophil cytolysis and extracellular trap cell death (ETosis) has predominantly been examined in non-neoplastic eosinophil-associated diseases, with a limited investigation in neoplasms. This current electron microscopy study examined the ultrastructural characteristics of eosinophil cytolysis and ETosis across four distinct gastric cancer cases: three cases (cases 1–3) exhibited non-ETotic cytolysis, while one case (case 4) presented eosinophils at various stages of ETosis. In cases 1–3, eosinophil non-ETotic cytolysis was characterized by localized plasma membrane disruption, the presence of free extracellular granules (FEGs), and the maintenance of a round or oval nuclear lobe profile. In case 4, eosinophils were observed in progressive stages of ETosis, arbitrarily subdivided into early, intermediate, and advanced. Although early ETosis and non-ETotic cytolysis exhibited overlapping ultrastructural features, chromatin decondensation and nuclear envelope enlargement were more pronounced in early ETosis. Nuclear envelope disruption, loss of the round or oval nuclear lobe profile (intermediate stage), extracellular DNA trap deposition, and the appearance of Charcot-Leyden crystals (advanced stage) were all distinctive features of ETosis. The findings of this case report confirm previous observations of eosinophil cytolysis with or without ETosis in non-neoplastic diseases and extend them to advanced gastric carcinoma. Since Charcot-Leyden crystals were only seen in case 4, their correlation with ETosis was further supported. In gastric cancer, the release of FEGs during non-ETotic cytolysis and the release of both FEGs and DNA traps during ETotic cytolysis may contribute to the formation of an antitumor microenvironment.

Immunotherapy has gathered significant attention and is now a widely used cancer treatment that uses the body’s immune system to fight cancer. Despite initial successes, its broader clinical application is hindered by limitations such as heterogeneity in patient response and challenges associated with the tumor immune microenvironment. Recent advancements in nanotechnology have offered innovative solutions to these barriers, providing significant enhancements to cancer immunotherapy. Nanotechnology-based approaches exhibit multifaceted mechanisms, including effective anti-tumor immune responses during tumorigenesis and overcoming immune suppression mechanisms to improve immune defense capacity. Nanomedicines, including nanoparticle-based vaccines, liposomes, immune modulators, and gene delivery systems, have demonstrated the ability to activate immune responses, modulate tumor microenvironments, and target specific immune cells. Success metrics in preclinical and early clinical studies, such as improved survival rates, enhanced tumor regression, and elevated immune activation indices, highlight the promise of these technologies. Despite these achievements, several challenges remain, including scaling up manufacturing, addressing off-target effects, and navigating regulatory complexities. The review emphasizes the need for interdisciplinary approaches to address these barriers, ensuring broader clinical adoption. It also provides insights into interdisciplinary approaches, advancements, and the transformative potential of nano-immunotherapy and promising results in checkpoint inhibitor delivery, nanoparticle-mediated photothermal therapy, immunomodulation as well as inhibition by nanoparticles and cancer vaccines.