Advances in radiotherapy enhancing the efficacy of immune checkpoint inhibitors in malignant

The introduction of immune checkpoint inhibitors (ICIs) has facilitated the elucidation of the mechanisms underlying the remote effects observed in tumor therapy and has demonstrated significant promise for treating several advanced tumors. However, the natural resistance of “cold tumors” remains a...

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Main Authors: Yao Liao, Jinjing Deng, Xiyue Yang, Decai Wang, Xiaobo Du
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1611036/full
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author Yao Liao
Yao Liao
Jinjing Deng
Xiyue Yang
Xiyue Yang
Decai Wang
Xiaobo Du
Xiaobo Du
author_facet Yao Liao
Yao Liao
Jinjing Deng
Xiyue Yang
Xiyue Yang
Decai Wang
Xiaobo Du
Xiaobo Du
author_sort Yao Liao
collection DOAJ
description The introduction of immune checkpoint inhibitors (ICIs) has facilitated the elucidation of the mechanisms underlying the remote effects observed in tumor therapy and has demonstrated significant promise for treating several advanced tumors. However, the natural resistance of “cold tumors” remains a challenge that ICIs alone cannot overcome. Radiotherapy (RT) has been shown to enhance anti-tumor immunity by generating in situ antigens or antigenic fragments derived from tumor cells and local immune cell DNA, thereby attracting more immune-presenting cells to the tumor site. This process promotes the conversion of immune cells into anti-tumor effector cells and enhances the efficacy of ICIs, most likely reflecting the mechanism of the abscopal effect (ABE). Alternatively, ABE achieves optimal efficacy when anti-tumor effects synergistically enhance systemic immunity. This review delineates the molecular mechanisms underlying the distant compartment effect and summarizes clinical studies on enhancing immune checkpoint inhibitors through various RT techniques.
format Article
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institution Kabale University
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publishDate 2025-07-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Oncology
spelling doaj-art-b2f5311431334fcdb4ea08f2e8ed8dbd2025-08-20T03:28:24ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-07-011510.3389/fonc.2025.16110361611036Advances in radiotherapy enhancing the efficacy of immune checkpoint inhibitors in malignantYao Liao0Yao Liao1Jinjing Deng2Xiyue Yang3Xiyue Yang4Decai Wang5Xiaobo Du6Xiaobo Du7Sichuan Clinical Research Center for Radiation and Therapy, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, Sichuan, ChinaDepartment of Oncology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, Sichuan, ChinaDepartment of Orthopedics, Sichuan Science City Hospital, Mianyang, Sichuan, ChinaSichuan Clinical Research Center for Radiation and Therapy, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, Sichuan, ChinaDepartment of Oncology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, Sichuan, ChinaDepartment of Urology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, Sichuan, ChinaSichuan Clinical Research Center for Radiation and Therapy, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, Sichuan, ChinaDepartment of Oncology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, Sichuan, ChinaThe introduction of immune checkpoint inhibitors (ICIs) has facilitated the elucidation of the mechanisms underlying the remote effects observed in tumor therapy and has demonstrated significant promise for treating several advanced tumors. However, the natural resistance of “cold tumors” remains a challenge that ICIs alone cannot overcome. Radiotherapy (RT) has been shown to enhance anti-tumor immunity by generating in situ antigens or antigenic fragments derived from tumor cells and local immune cell DNA, thereby attracting more immune-presenting cells to the tumor site. This process promotes the conversion of immune cells into anti-tumor effector cells and enhances the efficacy of ICIs, most likely reflecting the mechanism of the abscopal effect (ABE). Alternatively, ABE achieves optimal efficacy when anti-tumor effects synergistically enhance systemic immunity. This review delineates the molecular mechanisms underlying the distant compartment effect and summarizes clinical studies on enhancing immune checkpoint inhibitors through various RT techniques.https://www.frontiersin.org/articles/10.3389/fonc.2025.1611036/fullmalignant tumorsimmune checkpoint inhibitorsradiotherapytumor therapycold tumors
spellingShingle Yao Liao
Yao Liao
Jinjing Deng
Xiyue Yang
Xiyue Yang
Decai Wang
Xiaobo Du
Xiaobo Du
Advances in radiotherapy enhancing the efficacy of immune checkpoint inhibitors in malignant
Frontiers in Oncology
malignant tumors
immune checkpoint inhibitors
radiotherapy
tumor therapy
cold tumors
title Advances in radiotherapy enhancing the efficacy of immune checkpoint inhibitors in malignant
title_full Advances in radiotherapy enhancing the efficacy of immune checkpoint inhibitors in malignant
title_fullStr Advances in radiotherapy enhancing the efficacy of immune checkpoint inhibitors in malignant
title_full_unstemmed Advances in radiotherapy enhancing the efficacy of immune checkpoint inhibitors in malignant
title_short Advances in radiotherapy enhancing the efficacy of immune checkpoint inhibitors in malignant
title_sort advances in radiotherapy enhancing the efficacy of immune checkpoint inhibitors in malignant
topic malignant tumors
immune checkpoint inhibitors
radiotherapy
tumor therapy
cold tumors
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1611036/full
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AT jinjingdeng advancesinradiotherapyenhancingtheefficacyofimmunecheckpointinhibitorsinmalignant
AT xiyueyang advancesinradiotherapyenhancingtheefficacyofimmunecheckpointinhibitorsinmalignant
AT xiyueyang advancesinradiotherapyenhancingtheefficacyofimmunecheckpointinhibitorsinmalignant
AT decaiwang advancesinradiotherapyenhancingtheefficacyofimmunecheckpointinhibitorsinmalignant
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