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Review

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

by 1,2,3,4,* and 1,4,*
1
Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL 35233, USA
2
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35233, USA
3
Programs in Immunology, University of Alabama at Birmingham, Birmingham, AL 35233, USA
4
O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35233, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: Takuji Tanaka
Int. J. Mol. Sci. 2021, 22(22), 12295; https://doi.org/10.3390/ijms222212295
Received: 25 October 2021 / Revised: 10 November 2021 / Accepted: 12 November 2021 / Published: 14 November 2021
(This article belongs to the Special Issue Radiation Biology and Molecular Radiation Oncology)
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. View Full-Text
Keywords: radiotherapy; immunotherapy; interferon; IFN-γ; JAK; STAT radiotherapy; immunotherapy; interferon; IFN-γ; JAK; STAT
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MDPI and ACS Style

Shi, L.Z.; Bonner, J.A. Bridging Radiotherapy to Immunotherapy: The IFN–JAK–STAT Axis. Int. J. Mol. Sci. 2021, 22, 12295. https://doi.org/10.3390/ijms222212295

AMA Style

Shi LZ, Bonner JA. Bridging Radiotherapy to Immunotherapy: The IFN–JAK–STAT Axis. International Journal of Molecular Sciences. 2021; 22(22):12295. https://doi.org/10.3390/ijms222212295

Chicago/Turabian Style

Shi, Lewis Zhichang, and James A. Bonner. 2021. "Bridging Radiotherapy to Immunotherapy: The IFN–JAK–STAT Axis" International Journal of Molecular Sciences 22, no. 22: 12295. https://doi.org/10.3390/ijms222212295

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