Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy

J Exp Med. 2006 May 15;203(5):1259-71. doi: 10.1084/jem.20052494. Epub 2006 Apr 24.

Abstract

Radiotherapy is one of the most successful cancer therapies. Here the effect of irradiation on antigen presentation by MHC class I molecules was studied. Cell surface expression of MHC class I molecules was increased for many days in a radiation dose-dependent manner as a consequence of three responses. Initially, enhanced degradation of existing proteins occurred which resulted in an increased intracellular peptide pool. Subsequently, enhanced translation due to activation of the mammalian target of rapamycin pathway resulted in increased peptide production, antigen presentation, as well as cytotoxic T lymphocyte recognition of irradiated cells. In addition, novel proteins were made in response to gamma-irradiation, resulting in new peptides presented by MHC class I molecules, which were recognized by cytotoxic T cells. We show that immunotherapy is successful in eradicating a murine colon adenocarcinoma only when preceded by radiotherapy of the tumor tissue. Our findings indicate that directed radiotherapy can improve the efficacy of tumor immunotherapy.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / immunology*
  • Adenocarcinoma / therapy
  • Animals
  • Antigen Presentation / immunology
  • Antigen Presentation / radiation effects*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / immunology*
  • Colonic Neoplasms / therapy
  • Dose-Response Relationship, Radiation
  • Gamma Rays*
  • Gene Expression Regulation, Neoplastic / immunology
  • Gene Expression Regulation, Neoplastic / radiation effects
  • HLA-A2 Antigen / genetics
  • HLA-A2 Antigen / immunology*
  • Humans
  • Immunotherapy*
  • Mice
  • Mice, Transgenic
  • Peptides / immunology
  • Protein Biosynthesis / immunology
  • Protein Biosynthesis / radiation effects
  • Protein Kinases / immunology
  • Radiotherapy
  • T-Lymphocytes, Cytotoxic / immunology
  • TOR Serine-Threonine Kinases

Substances

  • HLA-A2 Antigen
  • Peptides
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse