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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Bibliographic Details
Published in:Trends in immunology Vol. 39; no. 8; pp. 644 - 655
Main Authors: Rodríguez-Ruiz, María E., Vanpouille-Box, Claire, Melero, Ignacio, Formenti, Silvia Chiara, Demaria, Sandra
Format: Journal Article
Language:English
Published: England Elsevier Ltd 01.08.2018
Elsevier Limited
Subjects:
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
Online Access:Get full text
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Summary: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.
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Co-first authors
ISSN:1471-4906
1471-4981
1471-4981
DOI:10.1016/j.it.2018.06.001