Bridging Radiotherapy to Immunotherapy: The IFN–JAK–STAT Axis

The unprecedented successes of immunotherapies (IOs) including immune checkpoint blockers (ICBs) and adoptive T-cell therapy (ACT) in patients with late-stage cancer provide proof-of-principle evidence that harnessing the immune system, in particular T cells, can be an effective approach to eradicat...

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Autores principales:	Lewis Zhichang Shi, James A. Bonner
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	radiotherapy immunotherapy interferon IFN-γ JAK STAT Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/186df8d319744d2c830cfb34d6ea2a78
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spelling	oai:doaj.org-article:186df8d319744d2c830cfb34d6ea2a782021-11-25T17:55:08ZBridging Radiotherapy to Immunotherapy: The IFN–JAK–STAT Axis10.3390/ijms2222122951422-00671661-6596https://doaj.org/article/186df8d319744d2c830cfb34d6ea2a782021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12295https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The unprecedented successes of immunotherapies (IOs) including immune checkpoint blockers (ICBs) and adoptive T-cell therapy (ACT) in patients with late-stage cancer provide proof-of-principle evidence that harnessing the immune system, in particular T cells, can be an effective approach to eradicate cancer. This instills strong interests in understanding the immunomodulatory effects of radiotherapy (RT), an area that was actually investigated more than a century ago but had been largely ignored for many decades. With the “newly” discovered immunogenic responses from RT, numerous endeavors have been undertaken to combine RT with IOs, in order to bolster anti-tumor immunity. However, the underlying mechanisms are not well defined, which is a subject of much investigation. We therefore conducted a systematic literature search on the molecular underpinnings of RT-induced immunomodulation and IOs, which identified the IFN–JAK–STAT pathway as a major regulator. Our further analysis of relevant studies revealed that the signaling strength and duration of this pathway in response to RT and IOs may determine eventual immunological outcomes. We propose that strategic targeting of this axis can boost the immunostimulatory effects of RT and radiosensitizing effects of IOs, thereby promoting the efficacy of combination therapy of RT and IOs.Lewis Zhichang ShiJames A. BonnerMDPI AGarticleradiotherapyimmunotherapyinterferonIFN-γJAKSTATBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12295, p 12295 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	radiotherapy immunotherapy interferon IFN-γ JAK STAT Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	radiotherapy immunotherapy interferon IFN-γ JAK STAT Biology (General) QH301-705.5 Chemistry QD1-999 Lewis Zhichang Shi James A. Bonner Bridging Radiotherapy to Immunotherapy: The IFN–JAK–STAT Axis
description	The unprecedented successes of immunotherapies (IOs) including immune checkpoint blockers (ICBs) and adoptive T-cell therapy (ACT) in patients with late-stage cancer provide proof-of-principle evidence that harnessing the immune system, in particular T cells, can be an effective approach to eradicate cancer. This instills strong interests in understanding the immunomodulatory effects of radiotherapy (RT), an area that was actually investigated more than a century ago but had been largely ignored for many decades. With the “newly” discovered immunogenic responses from RT, numerous endeavors have been undertaken to combine RT with IOs, in order to bolster anti-tumor immunity. However, the underlying mechanisms are not well defined, which is a subject of much investigation. We therefore conducted a systematic literature search on the molecular underpinnings of RT-induced immunomodulation and IOs, which identified the IFN–JAK–STAT pathway as a major regulator. Our further analysis of relevant studies revealed that the signaling strength and duration of this pathway in response to RT and IOs may determine eventual immunological outcomes. We propose that strategic targeting of this axis can boost the immunostimulatory effects of RT and radiosensitizing effects of IOs, thereby promoting the efficacy of combination therapy of RT and IOs.
format	article
author	Lewis Zhichang Shi James A. Bonner
author_facet	Lewis Zhichang Shi James A. Bonner
author_sort	Lewis Zhichang Shi
title	Bridging Radiotherapy to Immunotherapy: The IFN–JAK–STAT Axis
title_short	Bridging Radiotherapy to Immunotherapy: The IFN–JAK–STAT Axis
title_full	Bridging Radiotherapy to Immunotherapy: The IFN–JAK–STAT Axis
title_fullStr	Bridging Radiotherapy to Immunotherapy: The IFN–JAK–STAT Axis
title_full_unstemmed	Bridging Radiotherapy to Immunotherapy: The IFN–JAK–STAT Axis
title_sort	bridging radiotherapy to immunotherapy: the ifn–jak–stat axis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/186df8d319744d2c830cfb34d6ea2a78
work_keys_str_mv	AT lewiszhichangshi bridgingradiotherapytoimmunotherapytheifnjakstataxis AT jamesabonner bridgingradiotherapytoimmunotherapytheifnjakstataxis
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Bridging Radiotherapy to Immunotherapy: The IFN–JAK–STAT Axis

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