Patient-specific tumor peptide–Major Histocompatibility Complex class I (pMHC-I)

Patient-specific tumor peptide–MHC class I complexes are molecular structures found on the surface of malignant cells, formed by the association of a tumor-specific neoantigen (a peptide derived from a somatic mutation) with a Major Histocompatibility Complex (MHC) class I molecule. These complexes are fundamental to the adaptive immune system's ability to recognize and eliminate cancer, as they serve as the specific ligands for the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes. Because these peptides are derived from mutations unique to an individual's tumor, they are not present in healthy tissues, making them ideal targets for highly specific immunotherapies such as personalized cancer vaccines and TCR-engineered T-cell (TCR-T) therapies. The therapeutic goal is to prime or engineer the immune system to recognize these unique signatures, leading to the selective destruction of tumor cells while sparing normal cells. However, the effectiveness of targeting these complexes can be limited by the tumor's ability to downregulate MHC expression or the high degree of mutational heterogeneity within a single patient's metastatic sites.

Other names

Neoantigen-MHC class I complexTumor-specific antigen-HLA complexPersonalized neoantigen-peptide-MHC complexHLA-peptide complexTSA-MHC-I

Binding to T-cell receptors (TCRs) to trigger cytotoxic T-lymphocyte (CTL) mediated lysis of tumor cells.