Tumor-associated and tumor-specific antigen presented on MHC class I and II (TAA/TSA-MHC)

Tumor-associated antigens (TAAs) and tumor-specific antigens (TSAs) are peptide fragments derived from intracellular proteins that are displayed on the cell surface by Major Histocompatibility Complex (MHC) Class I and Class II molecules [PubMed: 30552151]. TAAs are proteins expressed in both normal and neoplastic tissues but are often overexpressed or aberrantly regulated in cancer, such as HER2, gp100, or MAGE-A4 [PubMed: 28972530]. In contrast, TSAs, or neoantigens, result from tumor-specific genomic alterations like point mutations, frameshifts, or viral integrations, making them unique to the tumor and highly specific targets for the immune system [PubMed: 29735922]. These peptide-MHC (pMHC) complexes are the fundamental units recognized by T-cell receptors (TCRs), forming the basis for various immunotherapies including cancer vaccines, TCR-engineered T cells, and bispecific T-cell engagers [PubMed: 33024320]. Therapeutic strategies targeting these complexes aim to harness the specificity of the adaptive immune system to selectively eliminate malignant cells while sparing healthy tissue [PubMed: 31515458]. However, challenges such as HLA downregulation and potential cross-reactivity with self-peptides remain significant hurdles in the development of these therapies [PubMed: 30224319].

Other names

Tumor-associated antigenTumor-specific antigenNeoantigenCancer-testis antigenpMHCPeptide-HLA complexTumor neoantigen

Recognition of peptide-MHC complexes by T-cell receptors (TCRs) or TCR-like antibodies to trigger T-cell mediated lysis of tumor cells.