title: Irradiation and immunotherapy: From concept to the clinic.
abstract: In recent years, an increased understanding of T-cell-regulatory mechanisms has led to the development of a novel class of immune-checkpoint inhibitors that have robust clinical activity against a broad array of malignancies-even those that historically were not believed to be sensitive to immune therapy. With this, there has been renewed interest in the potential for synergy with more traditional forms of anticancer therapy like radiation therapy (RT). The role of RT in palliation or as definitive treatment for certain malignancies has been well established. Yet, in recent years, the concept has come to light that RT could be an attractive partner for use in combination with other immunotherapies. The effects of RT include not only control of an irradiated tumor but also multiple immunomodulatory effects on both the tumor and the microenvironment, priming tumors for an immune-mediated response. Herein, the authors summarize relevant preclinical data and rationale supporting the synergy of combined RT and immunotherapy and highlight recent clinical work on promising combination strategies. Cancer 2016;122:1659-71. © 2016 American Cancer Society.
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke University, Durham, North Carolina.
authors.forename: April K S
authors.initials: AK
authors.lastname: Salama
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, New York.|Weill Cornell Medical College, New York, New York.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Postow
authors.affiliation: Department of Radiation Oncology, Duke University, Durham, North Carolina.
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Salama
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors*; D059447:Cell Cycle Checkpoints; D003131:Combined Modality Therapy / Q000379:methods; D016371:Cranial Irradiation / Q000379:methods; D006801:Humans; D007165:Immunosuppression Therapy; D007167:Immunotherapy / Q000379:methods*; D000074324:Ipilimumab; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011836:Radiation Tolerance; D016634:Radiosurgery / Q000379:methods; D011878:Radiotherapy / Q000379:methods*; D013601:T-Lymphocytes / Q000502:physiology; D059016:Tumor Microenvironment / Q000528:radiation effects
chemical_list: D000911:Antibodies, Monoclonal; D060890:B7-H1 Antigen; D060908:CTLA-4 Antigen; D000074324:Ipilimumab
keywords: cytotoxic T-lymphocyte-associated protein 4 (CTLA-4); immunotherapy; ipilimumab; programmed cell death 1/programmed death-ligand 1 (PD-1/PD-L1); radiotherapy