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

By E. Reits, J. Hodge, C. Herberts, T. Groothuis, M. Chakraborty, Elizabeth K.Wansley, K. Camphausen, R. Luiten, A. H. de Ru, J. Neijssen and 7 more. Journal of Experimental Medicine, 2006

1,684 citations recorded by the source corpus.

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 γ-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.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/ceb4dd74c9bd307408456e3eb558060feca05361

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Citations in the corpus

Immune parameters affecting the efficacy of chemotherapeutic regimens (2011, background): “Through their action on cancer cells, chemotherapeutics can restore or enhance the expression of tumor antigens, making them more recognizable to the immune system”
The Efficacy of Radiotherapy Relies Upon Induction of Type I Interferon-Dependent Innate and Adaptive Immunity (2011, neutral): “Cancer Res; 71(7) April 1, 2011 Cancer Research 2494”
Stereotactic Radiation Therapy Augments Antigen-Specific PD-1-Mediated Anti-Tumor Immune Responses via Cross-Presentation of Tumor Antigen (2014, background): “Studies from several research groups have shown that XRT increases the expression of MHC class I in a dose-dependentmanner in anumber of different tumor types (7, 12).”
Cancer despite immunosurveillance: immunoselection and immunosubversion (2006, background): “In addition, radiotherapy increases the expression of MHC class I molecules and improves antigen presentatio”
Clinical significance of tumor-infiltrating lymphocytes in breast cancer (2016, background): “These distant responses occur because the local cellular damage increases cellular stress signals and trigger type 1 cytokine release, recruiting antigen presenting cells to the tumor and improving antigen presentation of tumor antigens to T-cells converting the tumor an in situ vaccine [51, 52].”
Towards a systems understanding of MHC class I and MHC class II antigen presentation (2011, background): “The synthesis of proteins may be affected by various stimuli, such as interferon-γ (IFNγ), ionizing radiation (via mammalian target of rapamycin (mTOR) activation”
Combining radiotherapy and cancer immunotherapy: a paradigm shift. (2013, background): “Although radiation can promote homing and extravasation of effector T cells at the tumor site and induce the expression of molecules that enhance the recognition of the tumor by T cells (30,32,37,40,42,48), these steps are generally insufficient, thus explaining, in part, the rarity of abscopal effe”
Radiation and Dual Checkpoint Blockade Activates Non-Redundant Immune Mechanisms in Cancer (2015, positive): “Although the cause and consequence of these repertoire changes remain to be defined, RT can alter peptide presentation 20 , and CDR3 changes after M. tuberculosis infection have been hypothesized to be antigen-driven 15 .”