Tumor microenvironment activatable immunomodulator for cancer immunotherapy.

STING agonist-primed supramolecular oncolytic hydrogel vaccine for tuning tumors against themselves.

Engineering nanomedicine for STING pathway activation: Advancing cancer immunotherapy.

Advances in cancer immunotherapy: underlying the mechanisms of inflammasome regulation from preclinical and nutritional insights.

Albumin-bound alkylated resiquimod for enhanced cancer immunotherapy.

Adaptive resistance in cancer immunotherapy.

This review examines the advancements in cancer immunotherapies, particularly focusing on dendritic cell (DC)-based vaccines developed through in vitro methods. DCs are essential for connecting innate and adaptive immunity and serve as powerful antigen-presenting cells. They play an essential role in the anti-tumor immune response by activating cytotoxic T lymphocytes and natural killer cells. DC vaccines, which involve engineering DCs to express tumor-associated antigens and administering them to patients, potentially enhance the T-cell-mediated destruction of tumor cells. The review details the progression of DC vaccine preparation from simple antigenic peptide pulsing to advanced genetic modification and cell fusion techniques. It discusses the use of envelope fusogenic membrane glycoproteins and chemical agents, such as polyethylene glycol, to facilitate the fusion of DCs with tumor cells, creating fusion cell vaccines that exhibit anti-tumor efficacy in both preclinical and clinical settings. Recent developments of DC vaccines have utilized alternative vectors, addressing some limitations of previous vaccine generations. Additionally, the review examines the integration of DC vaccines with other immunotherapies to combat tumor-induced immunosuppression. Despite their potential, DC vaccines face challenges that necessitate further refinement of therapeutic strategies and clinical validation. In conclusion, this review underscores the pivotal role of DC vaccines in cancer therapy and elucidates ongoing endeavors to augment their efficacy via combination therapies and advanced preparation techniques.

STING-Activating Nanomedicines in Cancer Immunotherapy: Mechanisms, Design, and Therapeutic Outcomes.

In response to treatment with immune checkpoint inhibitors (ICIs), patients with cancer can develop immune-related adverse events (irAEs), which are off-target toxicities affecting non-tumour tissues. Development of an irAE can require cessation of ICI treatment and cause additional morbidities, unrelated to cancer. Although the mechanisms that drive irAEs remain largely unknown, thus limiting treatment strategies, emerging evidence implicates tissue microbiomes, particularly in the gastrointestinal tract, lung and skin, as potential mediators. Here we review evidence that supports roles for the microbiome in irAEs. We focus on ICI colitis, a common irAE that has strong association with the gut microbiome. We examine clinical and preclinical studies that shed light on the immune and microbial drivers of ICI colitis and discuss current experimental treatments. By summarizing recent findings, we aim to encourage research into therapies that reduce irAE risk and severity while preserving anti-tumour efficacy of ICI treatment.

Emerging advantages of nano delivery systems in enhancing CAR-T/CRISPR-Cas9 mediated cancer therapeutics.

Metabolites in the tumor microenvironment: Key drivers of immune cell fate and function as therapeutic targets in cancer.

Biological engineering has emerged since the 1980s as one of the most efficient technologies to develop new medicines. The monoclonal antibody platform is the most widely used, representing about 15-20% of drug sales. Only scarce and partial monoclonal antibody life cycle assessments (LCAs) are reported. We estimate the cradle-to-pharmacy gate carbon footprint of monoclonal antibodies from the pharmacopeia on the market (n = 103) using the full life cycle inventory of the medicines, encompassing antibody production, packaging production, transport, medicine manufacturing, and associated corporate emissions using a hybrid LCA/environmentally extended input-output model. Monoclonal antibody-based drugs have an important carbon footprint with a mean of 169.7 kgCO2e/vial or prefilled syringe (95% CI 10.1-621.1) and 371.4 kgCO2e/month (95% CI 23.1-1,479.5) vs. 14.1 kgCO2e/month (95% CI 0.33-36.2) for an oral treatment. A large fraction of emissions is emerging from corporate emissions. The 95% CI surrounding these estimations is about ±35%. Among subparts, antibody production emissions largely vary from 7.1 to 20,206 kgCO2e/g of antibody (mean 472 kgCO2e/g, 95% CI 8.2-2,529), depending on the production scale. As an illustration, the carbon footprint of second-line treatment options in rheumatoid arthritis ranges from 286 to 2,047 kgCO2e/year. In cancer immunotherapy, alternative weight-adjusted dosing strategies lead to a 10-20% mitigation in greenhouse gas emissions, while "low-dose" strategies may mitigate emissions by 2- to 10-fold. Antibody-based drugs have a significant carbon footprint, although highly variable. This database allows for a better understanding of the carbon footprint associated with these drugs, in order to better eco-design care pathways.

Cytokine-based NK cell engineering for cancer immunotherapy.

Immune checkpoint blockade, exemplified by anti-PD-L1 antibody (αPD-L1), has revolutionized cancer immunotherapy. Nevertheless, its therapeutic potential is constrained by the inherently low tumor immunogenicity and the persistence of cancer stem cells (CSCs), which drive immune escape and tumor recurrence. Here, a CSC-targeted, pH-sensitive liposomal nano-cocktail of doxorubicin and bufalin (PSLB/D), was demonstrated to elicit robust immunogenic cell death (ICD), thereby potentiating the efficacy of αPD-L1 in immunologically 'cold' triple-negative breast cancer (TNBC) models. The PSLB/D itself demonstrated potent synergistic tumor-inhibitory effects in both cell lines and 3-D tumor spheroids, and effectively eliminated CSCs, with 85-90% reductions in both primary and secondary sphere formation. Deep penetration and robust ICD-mediated immune response were observed in patient-derived organoids, highlighting its translational potential. The therapeutic efficacy was validated in immunocompromised MDA-MB-231 and immunocompetent 4T1 orthotopic mouse models. Notably, in immunocompetent 4T1 models, PSLB/D induced strong expression of calreticulin, leading to the recruitment of dendritic cells and cytotoxic CD8⁺ T cells. Activation of these immune cells converted the immunosuppressive 'cold' tumors into immunogenic 'hot' ones, substantially amplifying the effectiveness of αPD-L1. This chemo-immunotherapy also generated memory T cells, suggesting the potential for longer antitumor immune responses. STATEMENT OF SIGNIFICANCE: Cancer recurrence and immune evasion in triple-negative breast cancer (TNBC) are largely driven by resilient cancer stem cells (CSCs). This study introduces a pH-sensitive liposomal nano-cocktail composed of doxorubicin and a CSC inhibitor, specifically engineered to overcome the immunosuppressive tumor microenvironment. We demonstrate that this nanococktail triggers potent immunogenic cell death (ICD) in patient-derived organoids and orthotopic models, exceeding the efficacy of conventional formulations or monotherapy. By successfully converting "cold" TNBC tumors into immunologically "hot", the nano-cocktail significantly amplifies anti-PD-L1 immunotherapy outcomes. These findings offer a compelling evidence-based framework for integrating targeted nanomedicine with clinical chemo-immunotherapy protocols to prevent recurrence.

Thyroid cancer exhibits substantial heterogeneity in its tumor immune microenvironment (TIME), which critically shapes disease progression and therapeutic responsiveness. While most differentiated thyroid cancers (DTCs) remain indolent, a subset evolves into radioiodine-refractory disease or progresses to poorly differentiated (PDTC) and anaplastic thyroid carcinoma (ATC), characterized by aggressive behavior and limited treatment options. Emerging evidence suggests that this transition is accompanied by dynamic immune reprogramming rather than static immune evasion. In this review, we propose a stepwise model of immune evolution in thyroid cancer, spanning from autoimmune-driven inflammation in chronic lymphocytic thyroiditis (CLT) to immune-exhausted states in advanced tumors. We systematically characterize immune cell composition, functional states, and regulatory networks across disease stages, highlighting key shifts in antigen presentation, T-cell functionality, and myeloid cell polarization. Building on this framework, we integrate tumor immune phenotypes (“hot”, “altered”, and “cold”) with actionable biomarkers, including PD-L1 expression, tumor mutational burden, IFN-γ signatures, M2 macrophage-related signature, and tertiary lymphoid structures. We further map these immune contexts to rational therapeutic strategies, encompassing immune checkpoint blockade, combination regimens with tyrosine kinase inhibitors or radiotherapy, and emerging approaches such as innate immune activation and adoptive cell therapies. By linking immune evolution with therapeutic vulnerabilities, this review provides a translationally relevant framework for precision immunotherapy in thyroid cancer and highlights future directions for overcoming resistance in advanced disease.

A nanosystem targeting genomic instability and mitochondrial damage to stimulate STING pathway for synergistic immunotherapy for advanced prostate cancer.

Background Mast cells are increasingly recognized as an important regulator of the tumor microenvironment. However, their role in colorectal cancer (CRC) is controversial, and there is a lack of targetable mast cell-specific molecules to improve the tumor microenvironment and overcome resistance to immunotherapy. Methods We used single-cell RNA sequencing, bulk RNA sequencing, and bioinformatics analyses to characterize mast cell subsets in the CRC tumor microenvironment and assess their association with immunotherapy response. We further employed a murine orthotopic CRC model and multi-omics approaches to explore how mast cells regulate anti-tumor immunity. Results Tumor-infiltrating mast cells displayed altered transcriptional state in CRC and closely associated with tumor molecular features. Mast cell deficiency significantly attenuated tumor growth and increased immune cell infiltration in an orthotopic CRC model. Strikingly, a subset of mast cells specifically expressing cathepsin G (CTSG) correlated with immunotherapy resistance and poor prognosis in patient with CRC. Mast cell-derived CTSG contributed to tumor metabolic adaptation and limited chemokine-mediated immune recruitment. The interaction between mast cells and tumor cells was mainly mediated via protease-activated receptor 2 (PAR2) signaling. Furthermore, pharmacological inhibition of CTSG improved the recruitment and function of CD8 + T cell and enhanced the efficacy of anti-PD-1 in vivo . Conclusion Our findings uncover a pro-tumoral CTSG + mast cell subset associated with a metabolically active and immune-restricted microenvironment in CRC, and highlight CTSG as a promising target for improving immunotherapy response.

Radiotherapy and immunotherapy for advanced cancers: A meta-analysis of dose, sequencing, and survival patterns.

Advances in current and emerging immunotherapies for ovarian cancer.

Biomolecular condensates formed via phase separation are emerging targets for pharmacologic or genetic manipulation for cancer therapy. In this commentary, we envisage that further deciphering the composition and the physicochemical properties of oncogenic condensates will provide unprecedented opportunities to develop novel strategies for cancer chemotherapy and immunotherapy.