Antigen processing and presentation in cancer immunotherapy

Maxwell Y. Lee, Jun W. Jeon, Cem Sievers, Clint T. Allen

Research output: Contribution to journalReview articlepeer-review

Abstract

BACKGROUND: Knowledge 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. METHODS: Original articles covering antigen processing and presentation, epitope discovery, and in silico T cell epitope prediction were reviewed. RESULTS: Natural 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. CONCLUSIONS: Antigen 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.

Original languageEnglish (US)
JournalJournal for immunotherapy of cancer
Volume8
Issue number2
DOIs
StatePublished - Aug 1 2020

Keywords

  • T-lymphocytes
  • antigen presentation
  • antigens
  • immunotherapy
  • neoplasm

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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