title: Combination of radiotherapy and immune checkpoint inhibitors.
abstract: The ability of ionizing radiation to cause cell death and inflammatory reactions has been known since the beginning of its therapeutic use in oncology. However, only recently this property of radiation has attracted the attention of immunologists seeking to induce or improve antitumor immunity. As immune checkpoint inhibitors are becoming mainstream cancer treatments, radiation oncologists have begun to observe unexpected out-of-the-field (abscopal) responses in patients receiving radiation therapy during immunotherapy. These unexpected responses were predicted by experimental work in preclinical tumor models and have clear biological bases. Accumulating experimental evidence that radiation induces an immunogenic cell death and promotes recruitment and function of T cells within the tumor microenvironment supports the hypothesis that radiation can convert the tumor into an in situ individualized vaccine. This property of radiation is key to its synergy with immune checkpoint inhibitors, antibodies targeting inhibitory receptors on T cells such as cytotoxic T lymphocyte antigen-4 and programmed death-1. By removing the obstacles hindering the activation and function of antitumor T cells, these agents benefit patients with pre-existing antitumor immunity but are ineffective in patients lacking these spontaneous responses. Radiation induces antitumor T cells complementing the activity of immune checkpoint inhibitors.
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY.
authors.forename: Karsten A
authors.initials: KA
authors.lastname: Pilones
authors.affiliation: Department of Radiation Oncology, New York University School of Medicine, New York, NY.
authors.forename: Claire
authors.initials: C
authors.lastname: Vanpouille-Box
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY; Department of Radiation Oncology, New York University School of Medicine, New York, NY; NYU Laura and Isaac Perlmutter Cancer Center, New York, NY. Electronic address: sandra.demaria@nyumc.org.
authors.forename: Sandra
authors.initials: S
authors.lastname: Demaria
mesh_terms: D016923:Cell Death / Q000276:immunology / Q000528:radiation effects; D003131:Combined Modality Therapy / Q000379:methods; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000532:radiotherapy*; D011839:Radiation, Ionizing; D018714:Radiotherapy, Adjuvant / Q000379:methods; D059016:Tumor Microenvironment