Tumor neoantigen–Human Leukocyte Antigen complex (Neoantigen-HLA complex)

Tumor neoantigen–HLA complexes are molecular structures formed when mutated proteins unique to cancer cells are processed into short peptides and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules. These complexes serve as the primary signal for the adaptive immune system to distinguish malignant cells from healthy tissue, as neoantigens are not typically found in the normal human proteome. In a physiological context, these complexes are recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T cells and CD4+ helper T cells, initiating a targeted immune response against the tumor. Because neoantigens arise from somatic mutations, they are highly tumor-specific, making them ideal targets for precision immunotherapies such as personalized cancer vaccines and TCR-engineered T-cell (TCR-T) therapies. However, the therapeutic utility of these complexes is often challenged by the high degree of patient-specific variability in mutations and the potential for tumors to escape immune detection by downregulating HLA expression.

Other names

Neoepitope-HLA complexTumor-specific antigen-MHC complexpHLA complexMutant peptide-HLA complexTSA-HLA complex

Recognition by T-cell receptors (TCRs) or TCR-like antibodies to trigger T-cell mediated cytotoxicity and immune-driven tumor cell lysis.