title: Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy.
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.
authors.affiliation: Division of Tumor Biology, The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Reits
authors.forename: James W
authors.initials: JW
authors.lastname: Hodge
authors.forename: Carla A
authors.initials: CA
authors.lastname: Herberts
authors.forename: Tom A
authors.initials: TA
authors.lastname: Groothuis
authors.forename: Mala
authors.initials: M
authors.lastname: Chakraborty
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Wansley
authors.forename: Kevin
authors.initials: K
authors.lastname: Camphausen
authors.forename: Rosalie M
authors.initials: RM
authors.lastname: Luiten
authors.forename: Arnold H
authors.initials: AH
authors.lastname: de Ru
authors.forename: Joost
authors.initials: J
authors.lastname: Neijssen
authors.forename: Alexander
authors.initials: A
authors.lastname: Griekspoor
authors.forename: Elly
authors.initials: E
authors.lastname: Mesman
authors.forename: Frank A
authors.initials: FA
authors.lastname: Verreck
authors.forename: Hergen
authors.initials: H
authors.lastname: Spits
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schlom
authors.forename: Peter
authors.initials: P
authors.lastname: van Veelen
authors.forename: Jacques J
authors.initials: JJ
authors.lastname: Neefjes
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology / Q000528:radiation effects*; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology / Q000528:radiation effects; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology; D014176:Protein Biosynthesis / Q000276:immunology / Q000528:radiation effects; D011494:Protein Kinases / Q000276:immunology; D011878:Radiotherapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D058570:TOR Serine-Threonine Kinases
chemical_list: D015789:HLA-A2 Antigen; D010455:Peptides; D011494:Protein Kinases; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases