Immunological Mechanisms Responsible for Radiation-Induced Abscopal Effect

Radiotherapy has been used for more than a hundred years as a local tumor treatment. The occurrence of systemic antitumor effects manifesting as regression of tumors outside of the irradiated field (abscopal effect) was occasionally observed but deemed too rare and unpredictable to be a therapeutic...

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Vydané v:	Trends in immunology Ročník 39; číslo 8; s. 644 - 655
Hlavní autori:	Rodríguez-Ruiz, María E., Vanpouille-Box, Claire, Melero, Ignacio, Formenti, Silvia Chiara, Demaria, Sandra
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	England Elsevier Ltd 01.08.2018 Elsevier Limited
Predmet:	abscopal effect Animals Antitumor activity antitumor immunity Apoptosis Breast cancer Cancer Cancer therapies Combined Modality Therapy Deoxyribonucleic acid DNA DNA damage Humans Immune checkpoint Immune system Immunology Immunotherapy Immunotherapy - methods ionizing radiation Kinases Lymphocyte Activation Lymphocytes Lymphocytes T Mutation Neoplasm Metastasis Neoplasms - radiotherapy Proteins Radiation therapy Radiotherapy - methods T-Lymphocytes - immunology Tumor Burden tumor microenvironment Tumors abscopal effect tumor microenvironment antitumor immunity DNA damage ionizing radiation immunotherapy
ISSN:	1471-4906, 1471-4981, 1471-4981
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Abstract	Radiotherapy has been used for more than a hundred years as a local tumor treatment. The occurrence of systemic antitumor effects manifesting as regression of tumors outside of the irradiated field (abscopal effect) was occasionally observed but deemed too rare and unpredictable to be a therapeutic goal. This has changed with the advent of immunotherapy. Remarkable systemic effects have been observed in patients receiving radiotherapy to control tumors that were progressing during immune checkpoint blockade, stimulating interest in using radiation to overcome primary and acquired cancer resistance to immunotherapy. Here, we review the immunological mechanisms that are responsible for the ability of focal radiation to promote antitumor T cell responses that mediate tumor rejection and, in some cases, result in systemic effects. Tumor-targeted radiation occasionally elicits immune-mediated systemic tumor regression. Evidence of synergy between radiotherapy and immune checkpoint blockade (ICB) supports the concept of in situ vaccination by radiation, and ICB combinations together with an optimization of the radiation dose and fractionation offer paths to improved responses. Radiation alters the balance between immune-activating and -suppressive signals in the tumor microenvironment. Pathways involved in autoimmunity and microbial immunity are responsible for regulating the induction of type I interferon via cGAS/STING in irradiated tumors and are stimulated upon tumor cell irradiation and activation of the DNA damage response.
AbstractList	Radiotherapy has been used for more than a hundred years as a local tumor treatment. The occurrence of systemic antitumor effects manifesting as regression of tumors outside of the irradiated field (abscopal effect) was occasionally observed but deemed too rare and unpredictable to be a therapeutic goal. This has changed with the advent of immunotherapy. Remarkable systemic effects have been observed in patients receiving radiotherapy to control tumors that were progressing during immune checkpoint blockade, stimulating interest in using radiation to overcome primary and acquired cancer resistance to immunotherapy. Here, we review the immunological mechanisms that are responsible for the ability of focal radiation to promote antitumor T cell responses that mediate tumor rejection and, in some cases, result in systemic effects. Radiotherapy has been used for more than a hundred years as a local tumor treatment. The occurrence of systemic antitumor effects manifesting as regression of tumors outside of the irradiated field (abscopal effect) was occasionally observed but deemed too rare and unpredictable to be a therapeutic goal. This has changed with the advent of immunotherapy. Remarkable systemic effects have been observed in patients receiving radiotherapy to control tumors that were progressing during immune checkpoint blockade, stimulating interest in using radiation to overcome primary and acquired cancer resistance to immunotherapy. Here, we review the immunological mechanisms that are responsible for the ability of focal radiation to promote antitumor T cell responses that mediate tumor rejection and, in some cases, result in systemic effects.Radiotherapy has been used for more than a hundred years as a local tumor treatment. The occurrence of systemic antitumor effects manifesting as regression of tumors outside of the irradiated field (abscopal effect) was occasionally observed but deemed too rare and unpredictable to be a therapeutic goal. This has changed with the advent of immunotherapy. Remarkable systemic effects have been observed in patients receiving radiotherapy to control tumors that were progressing during immune checkpoint blockade, stimulating interest in using radiation to overcome primary and acquired cancer resistance to immunotherapy. Here, we review the immunological mechanisms that are responsible for the ability of focal radiation to promote antitumor T cell responses that mediate tumor rejection and, in some cases, result in systemic effects. Radiotherapy has been used for over hundred years as a local tumor treatment. The occurrence of systemic anti-tumor effects manifesting as regression of tumors outside of the irradiated field (abscopal effect) was occasionally observed but deemed too rare and unpredictable to be a therapeutic goal. This has changed with the advent of immunotherapy. Remarkable systemic effects have been observed in patients receiving radiotherapy to control tumors that were progressing during immune checkpoint blockade, stimulating interest in using radiation to overcome primary and acquired cancer resistance to immunotherapy. Here we review the immunological mechanisms that are responsible for the ability of focal radiation to promote antitumor T cell responses that mediate tumor rejection and, in some cases, result in systemic effects. Radiotherapy has been used for more than a hundred years as a local tumor treatment. The occurrence of systemic antitumor effects manifesting as regression of tumors outside of the irradiated field (abscopal effect) was occasionally observed but deemed too rare and unpredictable to be a therapeutic goal. This has changed with the advent of immunotherapy. Remarkable systemic effects have been observed in patients receiving radiotherapy to control tumors that were progressing during immune checkpoint blockade, stimulating interest in using radiation to overcome primary and acquired cancer resistance to immunotherapy. Here, we review the immunological mechanisms that are responsible for the ability of focal radiation to promote antitumor T cell responses that mediate tumor rejection and, in some cases, result in systemic effects. Tumor-targeted radiation occasionally elicits immune-mediated systemic tumor regression. Evidence of synergy between radiotherapy and immune checkpoint blockade (ICB) supports the concept of in situ vaccination by radiation, and ICB combinations together with an optimization of the radiation dose and fractionation offer paths to improved responses. Radiation alters the balance between immune-activating and -suppressive signals in the tumor microenvironment. Pathways involved in autoimmunity and microbial immunity are responsible for regulating the induction of type I interferon via cGAS/STING in irradiated tumors and are stimulated upon tumor cell irradiation and activation of the DNA damage response.
Author	Vanpouille-Box, Claire Rodríguez-Ruiz, María E. Formenti, Silvia Chiara Demaria, Sandra Melero, Ignacio
AuthorAffiliation	1 Division of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain 2 Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA 3 Sandra and Edward Meyer Cancer Center, New York, NY, USA 4 Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA
AuthorAffiliation_xml	– name: 1 Division of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain – name: 2 Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA – name: 4 Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA – name: 3 Sandra and Edward Meyer Cancer Center, New York, NY, USA
Author_xml	– sequence: 1 givenname: María E. surname: Rodríguez-Ruiz fullname: Rodríguez-Ruiz, María E. organization: Division of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain – sequence: 2 givenname: Claire surname: Vanpouille-Box fullname: Vanpouille-Box, Claire organization: Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA – sequence: 3 givenname: Ignacio surname: Melero fullname: Melero, Ignacio organization: Division of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain – sequence: 4 givenname: Silvia Chiara surname: Formenti fullname: Formenti, Silvia Chiara organization: Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA – sequence: 5 givenname: Sandra surname: Demaria fullname: Demaria, Sandra email: szd3005@med.cornell.edu organization: Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/30001871$$D View this record in MEDLINE/PubMed
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Snippet	Radiotherapy has been used for more than a hundred years as a local tumor treatment. The occurrence of systemic antitumor effects manifesting as regression of... Radiotherapy has been used for over hundred years as a local tumor treatment. The occurrence of systemic anti-tumor effects manifesting as regression of tumors...
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SubjectTerms	abscopal effect Animals Antitumor activity antitumor immunity Apoptosis Breast cancer Cancer Cancer therapies Combined Modality Therapy Deoxyribonucleic acid DNA DNA damage Humans Immune checkpoint Immune system Immunology Immunotherapy Immunotherapy - methods ionizing radiation Kinases Lymphocyte Activation Lymphocytes Lymphocytes T Mutation Neoplasm Metastasis Neoplasms - radiotherapy Proteins Radiation therapy Radiotherapy - methods T-Lymphocytes - immunology Tumor Burden tumor microenvironment Tumors
Title	Immunological Mechanisms Responsible for Radiation-Induced Abscopal Effect
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