Radiation Therapy Promotes Hepatocellular Carcinoma Immune Cloaking via PD-L1 Upregulation Induced by cGAS-STING Activation

Du, Shisuo; Chen, Genwen; Yang, Ping; Chen, Yi-Xing; Hu, Yong; Zhao, Qianqian; Zhang, Yang; Liu, Rong; Zheng, Dan-Xue; Zhou, Jian; Fan, Jia; Zeng, Zhao‐Chong

doi:10.1016/j.ijrobp.2021.12.162

Cited by 90 publications

(70 citation statements)

References 43 publications

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“…Preclinical studies have found that radiation can induce remodeling of the tumor immune microenvironment via multiple mechanisms, such as exosomes and stromal cells [49,50]. In the study by Du et al [51], RT was found to promote HCC immune cloaking through PD-L1 upregulation, which offered theoretical support for the combination of RT and immune check-point inhibitors (ICIs). In 2019, Yu et al [52] first identified the survival gain conferred by addition of RT to ICI therapy, which was further confirmed by the subsequent reports [53,54].…”

Section: Discussionmentioning

confidence: 99%

Systematic review of adjuvant external beam radiotherapy for hepatocellular carcinoma following radical hepatectomy

Wang

Lü²,

Ke³

et al. 2022

Radiotherapy and Oncology

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Section: Discussionmentioning

confidence: 99%

Systematic review of adjuvant external beam radiotherapy for hepatocellular carcinoma following radical hepatectomy

Wang

Lü²,

Ke³

et al. 2022

Radiotherapy and Oncology

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“…The programmed cell death protein 1 (PD-1) expressed by T cells binds to the ligand PD-L1 on the surface of tumor cells, which inhibits the clearance of tumor cells by effector T cells (60)(61)(62)(63). Activation of the cGAS-STING pathway has been demonstrated to increase the expression of PD-L1 on the surface of tumor cells and thus attenuate the activity of CTLs, which has been confirmed in models of liver cancer (64), melanoma (65), non-small cell lung cancer (NSCLC) (16) and small cell lung cancer (SCLC) (46,66). The antitumor effects of STING agonists were enhanced when combined with PD-L1 or PD-1 blockers (40,67,68).…”

Section: The Cgas-sting Pathway Has a Dichotomous Effect On The Recog...mentioning

confidence: 94%

Cancer immunotherapy strategies that target the cGAS-STING pathway

et al. 2022

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Activation of the cGAS-STING pathway by cytoplasmic DNA induces the production of Type-1 interferons. Recent advances in research suggest that the cGAS-STING pathway is involved in different parts of the cancer-immunity cycle (CIC) to promote or suppress antitumor immune responses. Combination therapy of STING agonists has made certain progress in preclinical as well as clinical trials, but the selection of combination therapy regimens remains a challenge. In this review, we summarize the role of the cGAS-STING in all aspects of CIC, and focus on the combination immunotherapy strategies of STING agonists and current unsolved challenges.

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“…Though the hypothesis that the damage signal released from tumor cells alone can activate a systemic antitumor immune response called the abscopal effect has been observed in a small-sample study (203), confirming the hypothesis without combining the signal with checkpoint inhibitors is difficult. The basic research revealed that RT may increase programmed death ligand 1 (PD-L1) levels in tumor and immune cells, contributing to immunosuppression and in part explaining the clinical success of the combination of RT with programmed cell death protein 1 (PD-1)/PD-L1 immunotherapy (216). As basic research data are available, more clinical trials regarding the combination of anti-PD-1/PD-L1 antibody with radiation are going on (217)(218)(219)(220).…”

Section: Targeting Rs Response Enhances Radiation Sensitivity By Inna...mentioning

confidence: 99%

Replication Stress: A Review of Novel Targets to Enhance Radiosensitivity-From Bench to Clinic

Zhang

Wang

et al. 2022

Front. Oncol.

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DNA replication is a process fundamental in all living organisms in which deregulation, known as replication stress, often leads to genomic instability, a hallmark of cancer. Most malignant tumors sustain persistent proliferation and tolerate replication stress via increasing reliance to the replication stress response. So whilst replication stress induces genomic instability and tumorigenesis, the replication stress response exhibits a unique cancer-specific vulnerability that can be targeted to induce catastrophic cell proliferation. Radiation therapy, most used in cancer treatment, induces a plethora of DNA lesions that affect DNA integrity and, in-turn, DNA replication. Owing to radiation dose limitations for specific organs and tumor tissue resistance, the therapeutic window is narrow. Thus, a means to eliminate or reduce tumor radioresistance is urgently needed. Current research trends have highlighted the potential of combining replication stress regulators with radiation therapy to capitalize on the high replication stress of tumors. Here, we review the current body of evidence regarding the role of replication stress in tumor progression and discuss potential means of enhancing tumor radiosensitivity by targeting the replication stress response. We offer new insights into the possibility of combining radiation therapy with replication stress drugs for clinical use.

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Radiation Therapy Promotes Hepatocellular Carcinoma Immune Cloaking via PD-L1 Upregulation Induced by cGAS-STING Activation

Cited by 90 publications

References 43 publications

Systematic review of adjuvant external beam radiotherapy for hepatocellular carcinoma following radical hepatectomy

Systematic review of adjuvant external beam radiotherapy for hepatocellular carcinoma following radical hepatectomy

Cancer immunotherapy strategies that target the cGAS-STING pathway

Replication Stress: A Review of Novel Targets to Enhance Radiosensitivity-From Bench to Clinic

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