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      Combining spatially fractionated radiation therapy (SFRT) and immunotherapy opens new rays of hope for enhancing therapeutic ratio

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          Highlights

          • •

            Spatially Fractionated Radiation Therapy (SFRT).

          • •

            Microvascular alterations.

          • •

            ‘RadScopal’ effect.

          • •

            Microbeam irradiation and showed significant abscopal effects in their bladders.

          • •

            Radiation-Induced Bystander Effect (RIBE).

          Abstract

          Spatially Fractionated Radiation Therapy (SFRT) is a form of radiotherapy that delivers a single large dose of radiation within the target volume in a heterogeneous pattern with regions of peak dosage and regions of under dosage. SFRT types can be defined by how the heterogeneous pattern of radiation is obtained. Immune checkpoint inhibitors (ICIs) have been approved for various malignant tumors and are widely used to treat patients with metastatic cancer. The efficacy of ICI monotherapy is limited due to the “cold” tumor microenvironment. Fractionated radiotherapy can achieve higher doses per fraction to the target tumor, and induce immune activation (immodulate tumor immunogenicity and microenvironment). Therefore, coupling ICI therapy and fractionated radiation therapy could significantly improve the outcome of metastatic cancer. This review focuses on both preclinical and clinical studies that use a combination of radiotherapy and ICI therapy in cancer.

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          Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC

          Scott J Antonia, Augusto Villegas, Davey Daniel … (2018)
          An earlier analysis in this phase 3 trial showed that durvalumab significantly prolonged progression-free survival, as compared with placebo, among patients with stage III, unresectable non-small-cell lung cancer (NSCLC) who did not have disease progression after concurrent chemoradiotherapy. Here we report the results for the second primary end point of overall survival.
          Article 0 comments Cited 904 times – based on 0 reviews     Review now
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            STING-Dependent Cytosolic DNA Sensing Promotes Radiation-Induced Type I Interferon-Dependent Antitumor Immunity in Immunogenic Tumors.

            Liufu Deng, Hua Jun Liang, Meng Meng Xu … (2014)
            Ionizing radiation-mediated tumor regression depends on type I interferon (IFN) and the adaptive immune response, but several pathways control I IFN induction. Here, we demonstrate that adaptor protein STING, but not MyD88, is required for type I IFN-dependent antitumor effects of radiation. In dendritic cells (DCs), STING was required for IFN-? induction in response to irradiated-tumor cells. The cytosolic DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS) mediated sensing of irradiated-tumor cells in DCs. Moreover, STING was essential for radiation-induced adaptive immune responses, which relied on type I IFN signaling on DCs. Exogenous IFN-? treatment rescued the cross-priming by cGAS or STING-deficient DCs. Accordingly, activation of STING by a second messenger cGAMP administration enhanced antitumor immunity induced by radiation. Thus radiation-mediated antitumor immunity in immunogenic tumors requires a functional cytosolic DNA-sensing pathway and suggests that cGAMP treatment might provide a new strategy to improve radiotherapy. Copyright © 2014 Elsevier Inc. All rights reserved.
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              Combining radiotherapy and cancer immunotherapy: a paradigm shift.

              Silvia Formenti, Sandra Demaria (2013)
              The therapeutic application of ionizing radiation has been largely based on its cytocidal power combined with the ability to selectively target tumors. Radiotherapy effects on survival of cancer patients are generally interpreted as the consequence of improved local control of the tumor, directly decreasing systemic spread. Experimental data from multiple cancer models have provided sufficient evidence to propose a paradigm shift, whereby some of the effects of ionizing radiation are recognized as contributing to systemic antitumor immunity. Recent examples of objective responses achieved by adding radiotherapy to immunotherapy in metastatic cancer patients support this view. Therefore, the traditional palliative role of radiotherapy in metastatic disease is evolving into that of a powerful adjuvant for immunotherapy. This combination strategy adds to the current anticancer arsenal and offers opportunities to harness the immune system to extend survival, even among metastatic and heavily pretreated cancer patients. We briefly summarize key evidence supporting the role of radiotherapy as an immune adjuvant. A critical appraisal of the current status of knowledge must include potential immunosuppressive effects of radiation that can hamper its capacity to convert the irradiated tumor into an in situ, individualized vaccine. Moreover, we discuss some of the current challenges to translate this knowledge to the clinic as more trials testing radiation with different immunotherapies are proposed.
              Article 0 comments Cited 380 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Weisi Yan
                Journal
                Journal ID (nlm-ta): Clin Transl Radiat Oncol
                Journal ID (iso-abbrev): Clin Transl Radiat Oncol
                Title: Clinical and Translational Radiation Oncology
                Publisher: Elsevier
                ISSN (Electronic): 2405-6308
                Publication date PMC-release: 20 October 2023
                Publication date Collection: January 2024
                Publication date (Electronic): 20 October 2023
                Volume: 44
                Electronic Location Identifier: 100691
                Affiliations
                [a ]Foshan Fosun Chancheng Hospital, P.R. China
                [b ]Baptist Health System, Lexington, KY, United States
                [c ]Junxin Precision Oncology Group, P.R. China
                [d ]Mayo Clinic Alix School of Medicine, Scottsdale, AZ, United States
                [e ]Albert Einstein Collage of Medicine New York, Center for Ion Therapy, Medaustron, Austria
                [f ]Department of Radiation Medicine Markey Cancer Center, University of Kentucky - College of Medicine, United States
                Author notes
                [* ]Corresponding author at: Baptist Health System, Lexington, KY, United States. weisiyan@ 123456gmail.com
                Article
                Publisher Item ID: S2405-6308(23)00116-7 Publisher ID: 100691
                DOI: 10.1016/j.ctro.2023.100691
                PMC ID: 10684810
                PubMed ID: 38033759
                SO-VID: b6ccf88c-f8f4-4d61-8e75-9d6f94b7fb99
                Copyright © © 2023 The Authors
                License:

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 12 July 2023
                Date revision received : 4 October 2023
                Date accepted : 15 October 2023
                Categories
                Subject: Review Article

                Keywords: sfrt,ribe,abscopal effect,immune checkpoint inhibitors (icis)
                Data availability:
                Keywords: sfrt, ribe, abscopal effect, immune checkpoint inhibitors (icis)

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