p53: An Immune Ecosystem Manipulator.

Abstract

Mutations in p53 are among the most common genetic abnormalities in cancer, and the loss of its normal function is a critical factor in cancer progression. In addition to autonomously inhibiting tumorigenesis, p53 mutations reshape the tumor immune microenvironment through various mechanisms. Thus, p53 acts as a critical mediator of immunotherapy resistance. This review elucidates how p53 mutations establish an "immune barrier network" by modulating secretomes (including cytokines and extracellular vesicles), immune ligands, antigen presentation, tumor metabolic reprogramming, and the extracellular matrix. Future research should focus on the specificity of mutant subtypes and organs, as well as their "double-edged sword" characteristics, which balance neoantigen generation and immune suppression, while exploring new strategies for combination immunotherapy that target the immune barrier network.