Reprogramming the Tumor–Immune Interface: CAR-T/NK, cGAS–STING, and ICI-Sensitizing Combinations

The resistance of solid tumors to immune-based therapies remains one of the most pressing challenges in oncology. Despite transformative advances in engineered cell therapies and immune checkpoint inhibitors (ICIs), durable responses are achieved in only a subset of patients. A central and unresolved question drives this collection: how can the tumor–immune interface be mechanistically reprogrammed to overcome immune resistance in solid tumors? Addressing this question demands both mechanistic insight and rationally designed combination strategies that target the barriers to immune recognition and response.This Research Topic provides a platform for advancing precision immuno-oncology by examining why immune therapies succeed in some patients and fail in others, and how tumors can be rendered more responsive to immune attack. Contributions are welcomed across a focused but interconnected scope, unified by the theme of overcoming immune resistance:Engineered and activated cell therapies — CAR-T and CAR-NK cell strategies for solid tumors, with a focus on overcoming tumor microenvironment (TME) barriers including hypoxia, antigen heterogeneity, T-cell exhaustion, and immunosuppressive signaling networksInnate immune activation — The role of the cGAS–STING pathway and related innate sensing mechanisms in reshaping the TME and enhancing responsiveness to adaptive immune therapiesICI-sensitizing strategies — Mechanism-based approaches that prime tumors for checkpoint blockade, including epigenetic reprogramming, metabolic modulation, and targeted co-treatmentsBiomarker-guided immunotherapy — Molecular and immune profiling strategies that enable patient stratification and predict response to combination regimens, particularly where resistance mechanisms can be prospectively identifiedTranslational and pre-clinical models — Innovative platforms that bridge laboratory findings to trial-ready therapeutic designs within the context of immune resistance in solid tumorsTo maintain a cohesive collection, submissions should engage directly with the mechanisms of immune resistance in solid tumors. Work focused on haematological malignancies, non-mechanistic clinical outcome reporting, or topics without a clear link to the TME or immune evasion falls outside the scope of this collection.This Topic welcomes original research articles, systematic reviews, meta-analyses, and perspective pieces that advance the translational understanding of tumor–immune interactions and inform next-generation immuno-oncology combinations. Topic editors: Shanchun Guo, MINGLI LIU Source: https://www.frontiersin.org/research-topics/79231/reprogramming-the-tumor-immune-interface-car-tnk-cgas-sting-and-ici-sensitizing-combinations