Patient-specific tumor-specific antigen–Major Histocompatibility Complex (TSA-MHC) on dendritic cells (TSA-MHC complex)

Patient-specific tumor-specific antigen–Major Histocompatibility Complex (TSA-MHC) complexes on dendritic cells are the fundamental units for initiating a personalized adaptive immune response against cancer. Dendritic cells (DCs) function as professional antigen-presenting cells that internalize tumor-specific neoantigens—proteins resulting from non-synonymous somatic mutations unique to an individual's tumor—and process them into peptides for display on MHC Class I and II molecules (Sahin & Türeci, 2018). This presentation allows for the precise priming of naive CD8+ and CD4+ T cells, which recognize the TSA-MHC complex via their specific T-cell receptors (TCRs) (Ott et al., 2017). Because these neoantigens are absent from the normal proteome, they serve as ideal targets for immunotherapy, minimizing the risk of central tolerance and off-target damage to healthy tissues (Hu et al., 2021). Therapeutic approaches leveraging this target include personalized mRNA vaccines and DC-based vaccines designed to expand the repertoire of tumor-reactive T cells. The success of these therapies depends on the accurate identification of immunogenic neoantigens and the efficient loading of these antigens onto the patient's own dendritic cells.

Other names

Neoantigen-MHC complexTumor-specific neoantigen-MHC complexPersonalized neoantigen-HLA complexTSA-HLA complex

Induction of tumor-specific T-cell responses via T-cell receptor (TCR) recognition of the neoantigen-MHC complex presented by dendritic cells (Sahin & Türeci, 2018; Ott et al., 2017).