Tumor Immune Evasion: Hiding as “Cold” Tumors and Resisting as “Hot” Tumors

Tumor evolution under immune pressure follows the logic of cancer immunoediting—elimination, equilibrium, and escape—in which immune surveillance removes highly immunogenic clones while selecting for variants capable of persistence and progression. Clinically, this evolutionary outcome is often operationalized as an immune-phenotype continuum, frequently simplified into “hot” (immune-inflamed) and “cold” (immune-excluded or immune-desert) tumors. This mini-review uses the provided schematic of elimination–equilibrium–escape (Figure 1) to organize tumor defense strategies into two archetypes: (i) immune hiding (“cold” tumors)—minimizing immune recognition through impaired priming, trafficking, and antigen presentation; and (ii) active immune resistance (“hot” tumors)—withstanding immune attack through adaptive checkpoint induction (e.g., PD-L1), immunosuppressive stromal/myeloid circuits, and genetic/epigenetic escape from interferon and antigen presentation pathways. We highlight mechanistic nodes that repeatedly govern the cold↔hot state and propose a practical framework to match intervention strategy to dominant failure mode: initiate immunity (convert cold to inflamed) versus release brakes (overcome adaptive resistance in hot tumors). We also briefly situate innate-like stress surveillance (e.g., NKG2D-mediated recognition) within immunoediting, emphasizing how tumors can evade both T cell– and NK cell–mediated control by altering ligand availability and microenvironmental context.