Radiation as an immunological adjuvant: current evidence on dose and fractionation

Radiation as an immunological adjuvant: current evidence on dose and fractionation

Ionizing radiation to a cancer site has the ability to convert the irradiated tumor in an immunogenic hub. However, radiation is a complex modifier of the tumor microenvironment and, by itself, is seldom sufficient to induce a therapeutically significant anti-tumor immune response, since it can also...

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Main Authors: Demaria, Sandra, Formenti, Silvia C.
Format: Online
Language:English
Published: Frontiers Media S.A. 2012
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481113/
id pubmed-3481113
recordtype oai_dc
spelling pubmed-34811132012-10-30 Radiation as an immunological adjuvant: current evidence on dose and fractionation Demaria, Sandra Formenti, Silvia C. Oncology Ionizing radiation to a cancer site has the ability to convert the irradiated tumor in an immunogenic hub. However, radiation is a complex modifier of the tumor microenvironment and, by itself, is seldom sufficient to induce a therapeutically significant anti-tumor immune response, since it can also activate immune suppressive pathways. While several combinations of local radiation and immunotherapy have been shown in pre-clinical models to induce powerful anti-tumor immunity, the optimal strategy to achieve this effect remains to be defined. When used in vivo, radiation effects on tumors depend on the dose per fraction applied, the number of fractions used, and the total dose. Moreover, the interplay of these three variables is contingent upon the tumor setting studied, both in pre-clinical and clinical applications. To enable repair of the collateral damage to the normal tissue, radiation is usually given in multiple fractions, usually of 2 Gy. Generally, the use of larger fractions is limited to stereotactic applications, whereby optimal immobilization reduces inter- and intrafraction movement and permits a very conformal delivery of dose to the target, with optimal exclusion of normal tissue. Translation of the partnership of radiation and immunotherapy to the clinic requires a careful consideration of the radiation regimens used. To date, little is known on whether different dose/fractionation regimens have a specific impact on the anti-tumor immune response. Most experiments combining the two modalities were conducted with single fractions of radiotherapy. However, there is at least some evidencethat when combined with some specific immunotherapy approaches, the ability of radiation to promote anti-tumor immunity is dependent on the dose and fractionation employed. We critically review the available in vitro and in vivo data on this subject and discuss the potential impact of fractionation on the ability of radiation to synergize with immunotherapy. Frontiers Media S.A. 2012-10-26 /pmc/articles/PMC3481113/ /pubmed/23112958 http://dx.doi.org/10.3389/fonc.2012.00153 Text en Copyright © http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) , which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Demaria, Sandra
Formenti, Silvia C.
spellingShingle Demaria, Sandra
Formenti, Silvia C.
Radiation as an immunological adjuvant: current evidence on dose and fractionation
author_facet Demaria, Sandra
Formenti, Silvia C.
author_sort Demaria, Sandra
title Radiation as an immunological adjuvant: current evidence on dose and fractionation
title_short Radiation as an immunological adjuvant: current evidence on dose and fractionation
title_full Radiation as an immunological adjuvant: current evidence on dose and fractionation
title_fullStr Radiation as an immunological adjuvant: current evidence on dose and fractionation
title_full_unstemmed Radiation as an immunological adjuvant: current evidence on dose and fractionation
title_sort radiation as an immunological adjuvant: current evidence on dose and fractionation
description Ionizing radiation to a cancer site has the ability to convert the irradiated tumor in an immunogenic hub. However, radiation is a complex modifier of the tumor microenvironment and, by itself, is seldom sufficient to induce a therapeutically significant anti-tumor immune response, since it can also activate immune suppressive pathways. While several combinations of local radiation and immunotherapy have been shown in pre-clinical models to induce powerful anti-tumor immunity, the optimal strategy to achieve this effect remains to be defined. When used in vivo, radiation effects on tumors depend on the dose per fraction applied, the number of fractions used, and the total dose. Moreover, the interplay of these three variables is contingent upon the tumor setting studied, both in pre-clinical and clinical applications. To enable repair of the collateral damage to the normal tissue, radiation is usually given in multiple fractions, usually of 2 Gy. Generally, the use of larger fractions is limited to stereotactic applications, whereby optimal immobilization reduces inter- and intrafraction movement and permits a very conformal delivery of dose to the target, with optimal exclusion of normal tissue. Translation of the partnership of radiation and immunotherapy to the clinic requires a careful consideration of the radiation regimens used. To date, little is known on whether different dose/fractionation regimens have a specific impact on the anti-tumor immune response. Most experiments combining the two modalities were conducted with single fractions of radiotherapy. However, there is at least some evidencethat when combined with some specific immunotherapy approaches, the ability of radiation to promote anti-tumor immunity is dependent on the dose and fractionation employed. We critically review the available in vitro and in vivo data on this subject and discuss the potential impact of fractionation on the ability of radiation to synergize with immunotherapy.
publisher Frontiers Media S.A.
publishDate 2012
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481113/
_version_ 1611918895770238976

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