This review addresses the major challenge in cancer immunotherapy posed by "cold" tumors, which resist treatment due to low immune cell infiltration and an immunosuppressive tumor microenvironment (TME). The authors meticulously examine the molecular and cellular mechanisms of this resistance, categorizing them into three "Cs": camouflage (impeding immune priming and infiltration), coercion (suppressing immune function), and cytoprotection (resisting inflammatory death). Crucially, the text evaluates numerous therapeutic strategies aimed at converting these refractory "cold" tumors into immunologically "hot" entities, discussing advancements such as epigenetic reprogramming, metabolic interventions, and the innovative use of biomaterials for localized drug delivery. Ultimately, the review frames the transformation of cold tumors to hot tumors as a critical pathway to broaden the efficacy of immune checkpoint inhibitors and other advanced immunotherapies.

References:

• Liu Y T, Wang Y L, Wang S, et al. Turning cold tumors into hot tumors to ignite immunotherapy[J]. Molecular Cancer, 2025, 24(1): 254.