title: Immunotherapy and stereotactic ablative radiotherapy (ISABR): a curative approach?
abstract: Conventional radiotherapy, in addition to its well-established tumoricidal effects, can also activate the host immune system. Radiation therapy modulates tumour phenotypes, enhances antigen presentation and tumour immunogenicity, increases production of cytokines and alters the tumour microenvironment, enabling destruction of the tumour by the immune system. Investigating the combination of radiotherapy with immunotherapeutic agents, which also promote the host antitumour immune response is, therefore, a logical progression. As the spectrum of clinical use of stereotactic radiotherapy continues to broaden, the question arose as to whether the ablative radiation doses used can also stimulate immune responses and, if so, whether we can amplify these effects by combining immunotherapy and stereotactic ablative radiotherapy (SABR). In this Perspectives article, we explore the preclinical and clinical evidence supporting activation of the immune system following SABR. We then examine studies that provide data on the effectiveness of combining these two techniques - immunotherapy and SABR - in an approach that we have termed 'ISABR'. Lastly, we provide general guiding principles for the development of future clinical trials to investigate the efficacy of ISABR in the hope of generating further interest in these exciting developments.
authors.affiliation: Division of Radiation Oncology, MD Anderson Cancer Center, Unit 97, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Bernstein
authors.affiliation: Division of Radiation Oncology, MD Anderson Cancer Center, Unit 97, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Sunil
authors.initials: S
authors.lastname: Krishnan
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, Building 10, Room 8B13, Bethesda, Maryland 20892-1750, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Hodge
authors.affiliation: Division of Radiation Oncology, MD Anderson Cancer Center, Unit 97, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Joe Y
authors.initials: JY
authors.lastname: Chang
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D005544:Forecasting; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D009369:Neoplasms / Q000628:therapy*; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D016634:Radiosurgery / Q000379:methods*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor