Tumor neoantigen-Major Histocompatibility Complex complex (NeoAg-MHC)

Tumor neoantigens presented on Major Histocompatibility Complex (MHC) molecules are highly specific therapeutic targets derived from somatic mutations unique to a patient's tumor (Schumacher & Schreiber, 2015). These mutations, which include single-nucleotide variants and frameshifts, produce novel protein sequences that are processed and displayed on the cell surface as peptide-MHC complexes (Blass & Ott, 2021). Because these neoepitopes are absent from the normal human proteome, they bypass central thymic tolerance and can be recognized as "foreign" by the host's T-cell receptors (TCRs) (Sahin & Türeci, 2018). This recognition triggers a targeted immune response, primarily mediated by CD8+ cytotoxic T cells, leading to the selective destruction of malignant cells while sparing healthy tissue (Zhang et al., 2021). Therapeutic interventions leveraging this target include personalized mRNA or peptide vaccines and adoptive cell therapies using TCR-engineered T cells (Ott et al., 2017). However, the clinical utility of these targets can be hindered by tumor-mediated immune evasion strategies, such as the downregulation of MHC expression or the loss of HLA heterozygosity (Garrido et al., 2016).

Other names

NeoepitopesTumor-specific antigens (TSA)Mutant peptide-HLA complexesMHC-restricted neoantigensTumor-specific neoantigens

T-cell receptor (TCR) mediated recognition of the neoantigen-MHC complex, triggering cytotoxic T lymphocyte (CTL) activation and subsequent tumor cell lysis (Schumacher & Schreiber, 2015).