Peptide-MHC I regulatory mechanisms and intervention strategies in anti-tumor T cell immunity

T cell immune responses are triggered by antigenic peptides presented through major histocompatibility complex class Is (pMHC-Is), which play an important role in the genesis, development, and therapy of tumors. The capacity of a specific pMHC-I to elicit T cell responses is deeply influenced by its expression level (quantity) and its immunogenicity (quality). Tumor cells can evade T cell immunity by down-regulating the quantity of pMHC-Is or selectively eliminating highly immunogenic antigenic peptides. Augmenting the quantity or quality of pMHC-Is is essential for tumor immunotherapy. However, the complexity of pMHC-I regulation and tumor heterogeneity pose challenges to clinical strategies. Consequently, developing approaches grounded in comprehensive analyses of pMHC-I regulatory mechanisms remains a focal point in the research of T cell immunity. In this review, we discuss how tumors modulate their surface pMHC-Is through genetic, epigenetic, and proteomic mechanisms and summarize potential therapeutic strategies targeting these mechanisms, which may provide a valuable reference for the development of novel tumor immunotherapies based on pMHC-I modulation. Tumor cells can achieve immune escape by interfering with the quantity and quality of pMHC-Is, and corresponding immunotherapy can also be achieved by the regulation of pMHC-Is.