Patient-specific tumor peptide–major histocompatibility complex (pMHC) (pMHC)

Patient-specific tumor peptide–major histocompatibility complex (pMHC) refers to the unique molecular signature formed when a neoantigen—a peptide derived from a tumor-specific somatic mutation—is presented on the cell surface by a Major Histocompatibility Complex molecule (Schumacher & Schreiber, 2015, Science). These complexes are fundamental to the cancer-immunity cycle, serving as the primary signal for T-cell receptors (TCRs) to identify and eliminate malignant cells while sparing healthy tissue (Chen & Mellman, 2013, Immunity). Because neoantigens are not encoded in the normal genome, they are not subject to central tolerance, allowing for the generation of high-affinity T-cell responses (Sahin & Türeci, 2018, Science). Therapeutic strategies targeting these complexes include personalized neoantigen vaccines, such as mRNA-4157, and adoptive cell therapies using TCR-engineered T cells designed to recognize specific pMHC combinations (Blass & Ott, 2021, Nature Reviews Clinical Oncology). Despite their potential, challenges include the high degree of tumor heterogeneity and the frequent downregulation of MHC expression by tumors as a mechanism of acquired resistance (Yarchoan et al., 2017, Nature Reviews Cancer).

Other names

Neoantigen-MHC complexTumor-specific antigen-MHC complexNeoepitope-HLA complexTumor-specific pMHCPersonalized neoantigen-HLA complex

Induction of antigen-specific T-cell responses through MHC-restricted recognition of tumor-specific neoepitopes by T-cell receptors (TCRs).