IL-17-responsive, tumor cell-intrinsic inflammatory programming remodels the tumor immune microenvironment toward an immunotherapy-permissive state. These findings establish IL-17-responsive tumor cell inflammatory programming as a mechanistic axis shaping immune checkpoint sensitivity and provide a rationale for biomarker-guided immunotherapy strategies.

In the preclinical study, durable antitumor effect was achieved through combination treatment with Olvi-Vec and cisplatin in mouse model of PROC. Combination therapy of Olvi-Vec and platinum-doublet chemotherapy resulted in a clinically meaningful benefit in the VIRO-15 study, reversing the typical trend of deteriorating PFS, and with clinical reversal of platinum resistance. Olvi-Vec treatment can favorably modify the TME in OC and may explain the apparent reversal of platinum resistance following platinum rechallenge.Trial Registration:ClinicalTrials.gov Identifier: NCT02759588.

In summary, BMDC-derived EVs loaded with antigen are potent immune stimulators, and removal of immune checkpoint molecules such as PD-L1 further enhances their immunogenicity. These findings support the development of engineered EVs as improved platforms for cancer immunotherapy.

By recreating patient-specific tumor-immune interactions ex vivo, our platform enables the discovery of therapeutic targets, the evaluation of immune responses, and validation in a patient-specific context. This approach demonstrates the feasibility of bridging a major gap in translational immunotherapy research and supports the development of personalized cancer immunotherapy strategies.

Interestingly, patients exhibiting co-high expression of stromal cell-derived CD39 rather than tumor cell-derived CD39 rather than tumor cell-derived CD39 with PD-L1 demonstrated optimal therapeutic outcomes. These findings suggest that CD39 and PD-L1 play critical roles in modulating the response to NIT and may serve as candidate biomarkers for guiding individualized treatment strategies in ESCC in the future.

This checkpoint modulation sensitized tumors to anti-PD-L1 and anti-CTLA-4 therapy, achieving synergistic tumor eradication and inducing durable, tumor-specific T-cell memory against tumor rechallenge. CNC018 represents a promising next-generation bacterial adjuvant with strong translational potential to safely enhance ICB efficacy in clinical cancer therapy.

Emerging therapies designed to transform cold tumors into immunologically active phenotypes through the modulation of cytokines and chemokines are discussed. Finally, the review highlights the ongoing challenges and future directions in using cytokine/chemokine modulation to overcome the limitations of current treatments, emphasizing their transformative potential in addressing the unmet needs of cancer immunotherapy.

By sono-sensitized immunotherapy, HA@Mn-MOF@E was demonstrated to inhibit orthotopic 4T1 tumor progression and induce tumor necrosis effectively. Such a designed bacterial sonosensitizer hybrid system offered the possibility of using sonodynamic assistance to sensitize live microorganisms-induced immunotherapy, with thorough activation of the antigen presentation in the tumor.

The surface-conjugated αPD-1 increases DC-T cell adhesion by 4.97-fold while amplifying the IFN-γ/IL-12 positive feedback loop, thereby potentiating T cell activity and augmenting effector T cells and other immune cells mediated anti-tumor efficacy. This multifunctional integration of adaptive DC therapy, nanoadjuvants and checkpoint blockade establishes an effective approach for next-generation DC therapy.

Checkpoint inhibitors are also under evaluation, particularly in combination with immunomodulatory or targeted agents. Collectively, these trials highlight both the promise and limitations of immunotherapy in pediatric sarcomas and underscore the need for deeper understanding of sarcoma immune biology to guide future, more effective therapeutic strategies.

However, cancer cells develop ferroptosis resistance through metabolic adaptations and antioxidant systems, complicating therapeutic strategies. Future studies should unravel context-specific regulatory networks linking ferroptosis, inflammation, and immunity to optimize immunotherapy efficacy.

Addition of oncolytic virus further augments the therapeutic activity of the combination regimen. Our study shows the molecular mechanism for regulating VCP expression by AR and suggests that inhibition of AR has the potential to increase the efficacy of immunotherapy in HCC.