Antigen processing and presentation in cancer immunotherapy

Abstract

BackgroundKnowledge about and identification of T cell tumor antigens may inform the development of T cell receptor-engineered adoptive cell transfer or personalized cancer vaccine immunotherapy. Here, we review antigen processing and presentation and discuss limitations in tumor antigen prediction approaches.MethodsOriginal articles covering antigen processing and presentation, epitope discovery, and in silico T cell epitope prediction were reviewed.ResultsNatural processing and presentation of antigens is a complex process that involves proteasomal proteolysis of parental proteins, transportation of digested peptides into the endoplasmic reticulum, loading of peptides onto major histocompatibility complex (MHC) class I molecules, and shuttling of peptide:MHC complexes to the cell surface. A number of T cell tumor antigens have been experimentally validated in patients with cancer. Assessment of predicted MHC class I binding and total score for these validated T cell antigens demonstrated a wide range of values, with nearly one-third of validated antigens carrying an IC50 of greater than 500 nM.ConclusionsAntigen processing and presentation is a complex, multistep process. In silico epitope prediction techniques can be a useful tool, but comprehensive experimental testing and validation on a patient-by-patient basis may be required to reliably identify T cell tumor antigens.

miRNAs and lncRNAs as Novel Therapeutic Targets to Improve Cancer Immunotherapy

“…Peptides are further edited by endoplasmic reticulum aminopeptidase1 (ERAP1) and loaded onto the MHC-I complex. If the affinity of the peptide for MHC-I is high, this complex will be transported first into the Golgi apparatus and then on the cell surface [ 46 ]. Furthermore, exogenous peptides, commonly presented in the MHC-II complex to TCD4+ lymphocytes, can be cross-presented to TCD8+ lymphocytes loaded onto the MHC-I complex in antigen presenting cells (APC).…”

Major Histocompatibility Complex Genes as Therapeutic Opportunity for Immune Cold Molecular Cancer Subtypes

“…These genes are involved in all critical steps from antigen processing and transport to antigen presentation, thus suggesting existence of biologically important relationships independent of cancer type. Our approach has allowed us to identify a group of 26 tumor subtypes with a concordant decrease of MHC expression when compared to other subtypes and corresponding normal adjacent tissues, which suggests neoantigen processing and presentation dysfunction as a route to escape from T cell-mediated immunosurveillance in these subtypes [48]. Furthermore, all MHClow subtypes displayed comparable levels of most of immunoinhibitors to normal tissue.…”

The Role of Antigen Processing and Presentation in Cancer and the Efficacy of Immune Checkpoint Inhibitor Immunotherapy

“…MHCI molecules have a groove that can preferentially bind 8-11mer peptides. The exposed surface of this groove where the antigenic epitope is bound is the part of the MHCI complex that is recognized by the TCR [ 58 ]. Peptides that enter the ER and are too long to fit into MHCI are trimmed by the concerted action of two ER-resident aminopeptidases, ERAP1 and ERAP2 [ 59 ].…”