Fractionated Radiation Therapy Stimulates Antitumor Immunity Mediated by Both Resident and Infiltrating Polyclonal T-cell Populations when Combined with PD-1 Blockade

• Published in: Clinical cancer research Vol. 23; no. 18; pp. 5514 - 5526
• Main Authors: Dovedi, Simon J, Cheadle, Eleanor J, Popple, Amy L, Poon, Edmund, Morrow, Michelle, Stewart, Ross, Yusko, Erik C, Sanders, Catherine M, Vignali, Marissa, Emerson, Ryan O, Robins, Harlan S, Wilkinson, Robert W, Honeychurch, Jamie, Illidge, Timothy M
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research Inc 15.09.2017
• Subjects: Animals; Anticancer properties; Antineoplastic Agents, Hormonal - pharmacology; Cancer; Cell Line, Tumor; Combined Modality Therapy; Cytokines - metabolism; Cytometry; Disease Models, Animal; Experimental design; Flow cytometry; Humans; Immune clearance; Immune response; Immunity; Immunogenicity; Infiltration; Lesions; Lymphocytes; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - drug effects; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Lymphocytes, Tumor-Infiltrating - radiation effects; Metastases; Mice; Monoclonal antibodies; Neoplasms - immunology; Neoplasms - metabolism; Neoplasms - pathology; Neoplasms - therapy; PD-1 protein; PD-L1 protein; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Programmed Cell Death 1 Receptor - metabolism; Radiation; Radiation therapy; Radiotherapy; Receptors, Antigen, T-Cell, alpha-beta - metabolism; Survival Rate; T cell receptors; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - radiation effects; Xenograft Model Antitumor Assays

Radiotherapy is a highly effective anticancer treatment forming part of the standard of care for the majority of patients, but local and distal disease recurrence remains a major cause of mortality. Radiotherapy is known to enhance tumor immunogenicity; however, the contribution and mechanisms of ra...