immunotherapy

Overview

Immunotherapy is a broad class of therapeutic approaches that harness, enhance, or redirect the immune system to recognize and control disease. In oncology, it is most commonly used to improve antitumor immune responses by activating T-lymphocytes, modulating dendritic cell function, reducing suppression by regulatory T cell populations, or blocking inhibitory pathways such as Programmed Death-Ligand 1 (PD-L1) and cytotoxic T-lymphocyte associated protein 4. More recently, immunotherapy has also been discussed in the context of immune-mediated neurologic disease and inflammatory conditions, reflecting its wider medical relevance beyond cancer.

Biologically, immunotherapy acts by shifting the balance between immune activation and immune evasion. Its effects are strongly influenced by the tumor microenvironment, including macrophage polarization, proinflammatory cytokine signaling, and the presence of immune checkpoints. In solid tumors, response can be shaped by tumor-intrinsic factors, immune infiltration, and interactions with the gut microbiome or human gut flora. Because of this complexity, immunotherapy is often studied in combination with radiotherapy, chemotherapy, Targeted therapies, or biologic agents such as pembrolizumab and durvalumab.

Focus of Latest Publications

Recent publications portray immunotherapy as a central strategy in contemporary cancer treatment, while also emphasizing its limitations and the need for rational combinations. In lung adenocarcinoma, one study examined whether lenvatinib could potentiate the antitumor efficacy of combined radiotherapy and PD-L1 blockade, noting that the potential synergy between lenvatinib, radiotherapy, and immunotherapy remained incompletely characterized. This reflects ongoing interest in combining tyrosine-kinase inhibitor therapy with checkpoint inhibitor-based regimens to improve response.

Several studies focused on the tumor immune microenvironment and immune resistance mechanisms. In esophageal squamous cell carcinoma, investigators highlighted the importance of exploring interactions between tumor cells and diverse immunological components inside the tumor immune microenvironment, as well as how immune checkpoint inhibitors may reshape that environment to create new therapeutic opportunities. A related thematic analysis of esophageal cancer immunotherapy described immunotherapy as a pivotal therapy with promising potential to improve survival rates and enable personalized care. Another publication on PD-1 and LAG-3 synergy emphasized that dual blockade of these pathways represents a promising strategy to overcome immunotherapy resistance, underscoring the importance of T-cell exhaustion biology in treatment design.

The gut microbiome emerged as a recurring modifier of immunotherapy response. In urothelial carcinoma, a review argued that increasing evidence suggests the gut microbiome plays a crucial role in cancer care, particularly when patients are treated with immunotherapy. This theme was extended by a phase I feasibility and safety study in refractory microsatellite-stable gastric cancer, where fecal bacteriotherapy was combined with anti-PD-1 therapy; the authors stated that the gut microbiome’s impact on immune modulation is a promising area for overcoming resistance to immunotherapy. Together, these studies support the idea that human gut flora may influence checkpoint inhibitor efficacy and that microbiome-directed interventions could complement pembrolizumab-class therapies.

Radiotherapy was repeatedly presented as an immunomodulatory partner. A review of immuno-radiotherapy concluded that the immunomodulatory potential of radiotherapy provides a strong rationale for combining it with immunotherapies and other immunostimulatory agents. In limited-stage small cell lung cancer, a prospective phase 2 trial evaluated durvalumab combined with concurrent chemoradiotherapy and noted that it remains unknown whether administering immunotherapy concurrently with chemoradiotherapy confers additional benefit. These reports indicate that timing, sequencing, and synergy remain active questions in combined-modality treatment.

Multiple publications addressed disease-specific challenges and resistance. In glioblastoma, a review noted that recent success using immunotherapies for other solid tumors has been largely unsuccessful in GBM, highlighting the difficulty of overcoming the immunosuppressive brain tumor microenvironment. In pancreatic ductal adenocarcinoma, a review stated that despite improvements in chemotherapy, targeted therapy, and immunotherapy, treatment remains challenging because of late diagnosis, drug resistance, and limited options. In cisplatin-resistant small cell lung cancer, immunotherapy was included among emerging therapeutic strategies being synthesized alongside targeted therapy and novel chemotherapeutic agents. In bladder cancer, neoadjuvant cisplatin-based chemotherapy with or without immunotherapy was described as standard of care, with pathologic complete response serving as a validated surrogate for survival after chemotherapy and a promising surrogate after other neoadjuvant treatments such as immunotherapy.

Research also explored immunotherapy in advanced prostate cancer and lung cancer. A nanosystem study in advanced prostate cancer described taxane-based chemotherapy and immunotherapy as standard treatments, while noting that efficacy is often limited by drug resistance and a cold tumor microenvironment. In lung cancer, a review on biomarkers in the era of radioimmunotherapy described immunotherapy as having improved lung cancer treatment over the past decade, and another article on lung cancer organoids discussed their applications in immunotherapy research, indicating a growing role for ex vivo models in evaluating response. Exosomes were also implicated in immune evasion and therapeutic resistance in lung cancer, including resistance to immunotherapy.

Beyond solid tumors, immunotherapy was also discussed in immune-mediated disease. A review of anti-N-methyl-d-aspartate receptor encephalitis stated that the disorder generally responds well to immunotherapy, with many patients achieving favorable clinical outcomes. This illustrates that immunotherapy can be effective in selected autoimmune or inflammatory neurologic conditions, not only malignancy.

Several studies focused on emerging biologic and engineered platforms intended to enhance immunotherapy. A review of multispecific immunoglobulins described bi- and multispecific antibodies as a rapidly advancing class of therapeutic biologics transforming oncology and immunotherapy. In melanoma, a metal-organic framework nanodrug designed to suppress “self” signals via CD47 blockade was reported as a promising strategy for enhancing immunotherapy. In T-cell acute lymphoblastic leukemia, BH3-mimetics and NK cell-mediated immunotherapy were presented as promising alone and in combination, warranting further preclinical and potential clinical evaluation. Another study on genomic instability and mitochondrial damage in advanced prostate cancer used a nanosystem to stimulate the STING1 pathway for synergistic immunotherapy, linking innate immune activation to therapeutic enhancement.

Across these publications, immunotherapy is consistently framed as a pivotal but context-dependent therapy. Its success appears to depend on tumor type, immune contexture, checkpoint biology, microbiome composition, and the ability to combine it rationally with radiotherapy, chemotherapy, Targeted therapies, or engineered delivery systems.

Key Publications

• Apr Discovery of biomarkers in the era of radioimmunotherapy against lung cancer: A bench-to-bedside promise. (International journal of cancer, 2026, PMID 41603296): "In the recent decade, immunotherapy has improved lung cancer treatment."
• Apr Construction and immunotherapy application of lung cancer organoids. (International journal of cancer, 2026, PMID 41676863): "It subsequently provides a summary and in-depth discussion on the culture methods, tumor microenvironment construction, and applications in immunotherapy of LCOs, aiming to contribute to the ongoing advancements in the field of lung cancer research."
• Apr Disease models of anti-N-methyl-d-aspartate receptor encephalitis: Investigating pathogenesis and targeted therapy. (Experimental neurology, 2026, PMID 41679588): "The disorder generally responds well to immunotherapy, with many patients achieving favorable clinical outcomes."
• Apr "Self" signal-suppressed metal-organic framework (MOF) nanodrug for enhanced immunotherapy of melanoma via CD47 blockade. (Colloids and surfaces. B, Biointerfaces, 2026, PMID 41723989): "These findings suggest that the MOF-based nanodrug represents a promising strategy for melanoma treatment with immune modulation to enhance therapeutic efficacy."
• Apr Exosome-mediated crosstalk between immune cells and tumor microenvironment in lung cancer: Implications for immune evasion and therapeutic resistance. (Cellular signalling, 2026, PMID 41759799): "Exosomes also make cells more resistant to chemotherapy, targeted treatment, and immunotherapy by changing the way cells send signals, changing the TME to help cells stay alive, and sending proteins that make cells more resistant."
• Apr Neoadjuvant Systemic Therapy in Kidney and Bladder Cancer: Current Evidence and Emerging Paradigms. (American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting, 2026, PMID 41774881): "In bladder cancer, neoadjuvant cisplatin-based chemotherapy with or without immunotherapy is standard of care, with pathologic complete response (pCR) serving as a validated surrogate for survival after chemotherapy and a promising potential surrogate for survival after other neoadjuvant treatments like immunotherapy."
• Apr HMGB3: A pivotal orchestrator of therapy resistance and cancer stemness in human malignancies (Review). (Oncology reports, 2026, PMID 41930588): "...thereby contributing to the resistance to chemotherapy, radiotherapy, targeted therapy and immunotherapy collectively."
• Apr A nanosystem targeting genomic instability and mitochondrial damage to stimulate STING pathway for synergistic immunotherapy for advanced prostate cancer. (Biomaterials, 2026, PMID 41628534): "Taxane-based chemotherapy and immunotherapy are standard treatments for advanced prostate cancer, yet their efficacy is often limited by drug resistance and an immunosuppressive, "cold" tumor microenvironment (TME)."
• Apr The making of multispecific immunoglobulins - a clinical perspective. (mAbs, 2026, PMID 41542910): "Over the past two decades, bi- and multispecific antibodies have emerged as a rapidly advancing class of therapeutic biologics, transforming oncology and immunotherapy."
• Apr Rationale and recommendations for improving early-stage oncology diagnosis, treatment, and access. (Journal of medical economics, 2026, PMID 41653456): "While effective new treatments for early-stage cancers have emerged, including immunotherapy and targeted therapies, barriers to reimbursement and access persist."