Tumor antigens presented on Major Histocompatibility Complex class I and II of dendritic cells (pMHC-DC)

Tumor antigens presented on Major Histocompatibility Complex (MHC) class I and II molecules of dendritic cells (DCs) are the fundamental units for initiating adaptive anti-tumor immunity (Wculek et al., 2020, Nature Reviews Immunology). Dendritic cells act as professional antigen-presenting cells that capture tumor-derived proteins, process them into peptides, and display them on MHC molecules to prime CD8+ cytotoxic and CD4+ helper T cells (Gardner & Ruffell, 2016, Trends in Immunology). This target is central to the efficacy of cancer vaccines and cellular therapies, which aim to enhance the density and diversity of these peptide-MHC complexes to overcome tumor-induced immunosuppression (Sahin & Türeci, 2018, Science). In many cancers, the presentation of these antigens is compromised by the tumor microenvironment or genetic loss of MHC components, leading to immune escape (Jhunjhunwala et al., 2021, Nature Reviews Cancer). Therapeutic strategies like Sipuleucel-T utilize ex vivo loaded DCs to present specific antigens, while neoantigen vaccines target unique mutations presented on the patient's MHC (Kantoff et al., 2010, NEJM). The primary safety concern involves on-target, off-tumor toxicity, where the immune system attacks healthy tissues expressing similar antigens (Linette et al., 2013, Blood). Successful targeting requires precise patient selection based on biomarkers like HLA genotype and tumor mutational burden (Schumacher & Schreiber, 2015, Science).

Other names

Tumor-associated antigen-MHC complexesNeoantigen-MHC complexespMHC complexes on APCsTumor-derived peptide-MHC complexes

Induction of tumor-specific T-cell responses through professional antigen presentation.