Background/Aims The abscopal effect, a rare phenomenon induced by radiation, can be reinforced by immunotherapy. Although radiation therapy and immunotherapy are increasingly being utilized for the treatment of hepatocellular carcinoma (HCC), whether immunotherapy could boost the abscopal effect remains unclear. In this study, we aimed to elucidate the immunological mechanisms underlying the abscopal effect induced by the combination of irradiation and immunotherapy in a murine HCC model.
Methods A syngeneic HCC mouse model was established by transplanting murine Hepa 1–6 HCC cells into both hind legs of immunocompetent C57BL/6 mice. The tumors on the right hind legs were irradiated, and abscopal effects were observed in the non-irradiated tumors on the left hind leg with or without the coadministration of anti-programmed cell death 1 (PD-1) antibodies. Flow cytometric analyses were performed to analyze the distributions of immune cells infiltrating both irradiated and non-irradiated tumors and the tumor-draining lymph nodes (TDLNs).
Results Administration of 16 Gy in two fractions more effectively inhibited the growth of both irradiated and nonirradiated tumors with higher tumor infiltration of cytotoxic T cells than 8 Gy did in a single fraction. The higher dose also increased activated dendritic cells in TDLNs, which had higher expression of the programmed cell death ligand 1. Coadministration of anti-PD-1 antibodies significantly enhanced the abscopal effect and increased infiltration of activated cytotoxic T cells in both irradiated and non-irradiated tumors.
Conclusions Our findings show that adding anti-PD-1 therapy to radiation enhanced the abscopal effect in a syngeneic murine model of HCC.
Citations
Citations to this article as recorded by
Immune Predictors of Radiotherapy Outcomes in Cervical Cancer Linghao Wang, Jie Zhu, Zequn Ding, Zhiyuan Xie, Xingchen Liu, Feihong Zhang, Xiaojun Liu, Yan Zhang, Haiyan Chen Advanced Science.2026;[Epub] CrossRef
Case Report: Pathologic complete response to PRaG therapy in an elderly patient with refractory metastatic gastric cancer Jun Lv, Fayi Yu, Linjiang Pan, Yeying Fang, Zhenghong Zhong, Xue Bai, Jinbiao Gao, Zhuxin Wei Frontiers in Oncology.2026;[Epub] CrossRef
Clinical Characteristics of Patients With Advanced Hepatocellular Carcinoma Who Transitioned to Subsequent Therapies Following Systemic Therapy Kenji Imai, Koji Takai, Masashi Aiba, Shinji Unome, Takao Miwa, Tatsunori Hanai, Hiroyasu Sakai, Yohei Shirakami, Atsushi Suetsugu, Masahito Shimizu Cancer Medicine.2026;[Epub] CrossRef
Nervous and immune system crosstalk shapes cancer progression and treatment response Mustafa TArdah, Raghda AliBakr, H. Malathi, Vimal Arora, Priya PriyadarshiniNayak, Dilbar Urazbaeva, Mukhayya Djumaniyazova, Sadullayeva Moxinur, Farid KarkonShayan Discover Oncology.2026;[Epub] CrossRef
Immune microenvironment and immunotherapy in hepatocellular carcinoma: mechanisms and advances Dong Xie, Yang Liu, Fangbiao Xu, Zhibo Dang, Mengge Li, Qinsheng Zhang, Zhongqin Dang Frontiers in Immunology.2025;[Epub] CrossRef
Radiosensitization strategies for hepatocellular carcinoma: Mechanisms, therapeutic advances, and clinical perspectives Jiahui Yang, Rong Chen Critical Reviews in Oncology/Hematology.2025; 213: 104773. CrossRef
Stereotactic body radiation therapy (SBRT) increases anti-PD-1 antitumor activity by enhancing the tumor immune microenvironment in mice with metastatic hepatocellular carcinoma Ke Xu, Tao Gu, Ke Su, Xin Liu, Bingsheng He, Jie He, Hao Chi, Xuancheng Zhou, Hanlin Liu, Rui Xiao, Xue Tang, Qinni Ye, Xue Zhou, Yingpeng Liu, Jie Xiong, Pan Wang, Han Li, Kun He, Lu Guo, Yunwei Han Discover Oncology.2025;[Epub] CrossRef
Sorafenib with or without co-interventions for hepatocellular carcinoma Shanshan Chen, Jian Ping Liu, Xinyu Li, Shoutao Dang, Wei Li Cochrane Database of Systematic Reviews.2025;[Epub] CrossRef
Recent Advances in Combination Therapy of YAP Inhibitors with Physical Anti-Cancer Strategies Junchi Zhou, Changyan Yu, Wanhong Yang, Nian Jiang, Sanhua Li, Yun Liu, Xinting Zhu Biomolecules.2025; 15(7): 945. CrossRef
Role of immune checkpoint inhibitor combinations in resectable and unresectable, embolization-eligible hepatocellular carcinoma Brandon M. Meyers, Howard J. Lim, Mayur Brahmania, Dave M. Liu, Vincent C. Tam, Deanna McLeod, Ravi Ramjeesingh, Jennifer J. Knox, Arndt Vogel Therapeutic Advances in Medical Oncology.2025;[Epub] CrossRef
Synergies between radiotherapy and immunotherapy: a systematic review from mechanism to clinical application JingLong Jiang, HouZe Li, QingCui Ma, Jing Liu, Fu Ren, YingQiu Song, TianLu Wang, KeYan Li, Ning Li Frontiers in Immunology.2025;[Epub] CrossRef
Local therapy overcomes primary resistance to target-immunotherapy combination in unresectable hepatocellular carcinoma Xiangqi Chen, Mingjian Piao, Zixiang Zhou, Shanshan Wang, Shuofeng Li, Nan Zhang, Boyu Sun, Kai Liu, Xu Yang, Xiaobo Yang, Xiaohua Shi, Chengpei Zhu, Haitao Zhao Cancer Immunology, Immunotherapy.2025;[Epub] CrossRef
Immunotherapy change overcomes acquired resistance after chemo-immunotherapy in unresectable biliary tract cancer Xiangqi Chen, Zixiang Zhou, Shuofeng Li, Guanhua Yu, Shi Feng, Ze Zhou, Boyu Sun, Shanshan Wang, Kai Liu, Chengjie Li, Mingjian Piao, Mingming Wang, Yihong Zhang, Hu Li, Chengpei Zhu, Zhenyu Zhu, Haitao Zhao Cancer Immunology, Immunotherapy.2025;[Epub] CrossRef
Molecular mechanisms underlying the abscopal effect induced by radiotherapy and its synergistic translational potential with immunotherapy Xinyi Chen, Mu Yang, Yongbiao Huang, Jingyao Tu, Yuwen Cai, Xianglin Yuan Therapeutic Advances in Medical Oncology.2025;[Epub] CrossRef
Multidisciplinary treatment for patients with advanced hepatocellular carcinoma complicated by Vp4 portal vein tumor thrombosis: Combination of atezolizumab and bevacizumab after hepatic arterial infusion chemotherapy and radiotherapy: A case series Kenji Yamaoka, Tomokazu Kawaoka, Yasutoshi Fujii, Shinsuke Uchikawa, Hatsue Fujino, Takashi Nakahara, Atsushi Ohno, Eisuke Murakami, Daiki Miki, Masataka Tsuge, Keigo Chosa, Kazuo Awai, Junichi Hirokawa, Yasushi Nagata, Shiro Oka Medicine: Case Reports and Study Protocols.2024; 5(6): e00325. CrossRef
Enhancing Magnetic Hyperthermia Efficacy through Targeted Heat Shock Protein 90 Inhibition: Unveiling Immune-Mediated Therapeutic Synergy in Glioma Treatment Ruby Gupta, Anjali Chauhan, Tashmeen Kaur, Bijoy Kumar Kuanr, Deepika Sharma ACS Nano.2024; 18(26): 17145. CrossRef
Lymphatic system regulation of anti-cancer immunity and metastasis Pin-Ji Lei, Cameron Fraser, Dennis Jones, Jessalyn M. Ubellacker, Timothy P. Padera Frontiers in Immunology.2024;[Epub] CrossRef
Research Progress on Dendritic Cells in Hepatocellular Carcinoma Immune Microenvironments Wenya Li, Guojie Chen, Hailin Peng, Qingfang Zhang, Dengyun Nie, Ting Guo, Yinxing Zhu, Yuhan Zhang, Mei Lin Biomolecules.2024; 14(9): 1161. CrossRef
Evaluation of Treatments with Radiotherapy Alone and Radiotherapy Plus Chemo-immunotherapy in Patients with Primary Liver Cancer based on Blood Biomarkers Shigao Huang, Yutian Yin, Jianping Li, Mei Shi, Huijie Bian, Lina Zhao Current Medicinal Chemistry.2024; 31(40): 6586. CrossRef
Novel VEGFR2 inhibitors with thiazoloquinoxaline scaffold targeting hepatocellular carcinoma with lower cardiotoxic impact Reham M. M. El-Hazek, Nashwa H. Zaher, Mostafa G. M. El-Gazzar, Noha A. Fadel, Walaa A. El-Sabbagh Scientific Reports.2023;[Epub] CrossRef
The paradoxical role of radiation‐induced cGAS–STING signalling network in tumour immunity Xiaoyi Zhang, Han Zhang, Jiajia Zhang, Mengdie Yang, Mengqin Zhu, Yuzhen Yin, Xin Fan, Fei Yu Immunology.2023; 168(3): 375. CrossRef
Comparison of stereotactic body radiotherapy with and without lenvatinib for advanced hepatocellular carcinoma: a propensity score analysis Quan Wang, Xiaoquan Ji, Jing Sun, Wengang Li, Xuezhang Duan, Aimin Zhang Journal of Cancer Research and Clinical Oncology.2023; 149(10): 7441. CrossRef
Hepatocellular carcinoma (HCC) immunotherapy by anti-PD-1 monoclonal antibodies: A rapidly evolving strategy Marzieh Nikoo, Zahraa F. Hassan, Mahsa Mardasi, Elmira Rostamnezhad, Fatemeh Roozbahani, Sahel Rahimi, Javad Mohammadi Pathology - Research and Practice.2023; 247: 154473. CrossRef
Combined radiotherapy and immune checkpoint inhibition for the treatment of advanced hepatocellular carcinoma Alexander H. Shannon, Ashish Manne, Dayssy A. Diaz Pardo, Timothy M. Pawlik Frontiers in Oncology.2023;[Epub] CrossRef
Radiation and Immune Checkpoint Inhibitors: Combination Therapy for Treatment of Hepatocellular Carcinoma Perla Chami, Youssef Diab, Danny N. Khalil, Hassan Azhari, William R. Jarnagin, Ghassan K. Abou-Alfa, James J. Harding, Joseph Hajj, Jennifer Ma, Maria El Homsi, Marsha Reyngold, Christopher Crane, Carla Hajj International Journal of Molecular Sciences.2023; 24(23): 16773. CrossRef
Inducing the Abscopal Effect in Liver Cancer Treatment: The Impact of Microwave Ablation Power Levels and PD-1 Antibody Therapy Changli Liao, Guiyuan Zhang, Ruotong Huang, Linyuan Zeng, Bin Chen, Haitao Dai, Keyu Tang, Run Lin, Yonghui Huang Pharmaceuticals.2023; 16(12): 1672. CrossRef
Prognostic significance of albumin–bilirubin score in patients with unresectable hepatocellular carcinoma undergoing combined immunotherapy and radiotherapy Dezuo Dong, Xianggao Zhu, Hongzhi Wang, Lijuan Li, Meng Wan, Shuai Li, Yangzi Zhang, Jianhao Geng, Yongheng Li, Weihu Wang Journal of Medical Imaging and Radiation Oncology.2022; 66(5): 662. CrossRef
Neoadjuvant Approaches in Hepatocellular Carcinoma: There's No Time Like the Present Joseph W. Franses, Andrew X. Zhu Clinical Cancer Research.2022; 28(13): 2738. CrossRef
Crosstalk between tumor-associated macrophages and neighboring cells in hepatocellular carcinoma Pil Soo Sung Clinical and Molecular Hepatology.2022; 28(3): 333. CrossRef
Combining stereotactic body radiotherapy with camrelizumab for unresectable hepatocellular carcinoma: a single-arm trial Jian-Xu Li, Ting-Shi Su, Wen-Feng Gong, Jian-Hong Zhong, Liu-Ying Yan, Jie Zhang, Li-Qing Li, Mei-Ling He, Rui-Jun Zhang, You-Qin Du, Xiao-Ting Wang, Shi-Xiong Liang, Bang-De Xiang Hepatology International.2022; 16(5): 1179. CrossRef
PD-1/PD-L1 checkpoint inhibitors in advanced hepatocellular carcinoma immunotherapy Qian Li, Jingjing Han, Yonglin Yang, Yu Chen Frontiers in Immunology.2022;[Epub] CrossRef
An Abscopal Effect in a Gastric Cancer Patient Treated with Combined Chemoimmunotherapy and Palliative Radiotherapy Zengtao Bao, Qiang Tang, Huiyu Chen, Baoming Zhang, Wenchao Shi, Dezhi Gu Immunotherapy.2022; 14(18): 1429. CrossRef
Exploring the mythical abscopal effect: Radiation and programmed cell death protein 1 (PD-1) blockade for hepatocellular carcinoma Jun Won Kim, Ik Jae Lee Clinical and Molecular Hepatology.2021; 27(1): 103. CrossRef
Manganese Ferrite Nanoparticles Enhance the Sensitivity of Hepa1-6 Hepatocellular Carcinoma to Radiation by Remodeling Tumor Microenvironments Sung-Won Shin, Kyungmi Yang, Miso Lee, Jiyoung Moon, Arang Son, Yeeun Kim, Suha Choi, Do-hyung Kim, Changhoon Choi, Nohyun Lee, Hee Chul Park International Journal of Molecular Sciences.2021; 22(5): 2637. CrossRef
Immunogenic Cell Death Induction by Ionizing Radiation Mengqin Zhu, Mengdie Yang, Jiajia Zhang, Yuzhen Yin, Xin Fan, Yu Zhang, Shanshan Qin, Han Zhang, Fei Yu Frontiers in Immunology.2021;[Epub] CrossRef
Current role of proton beam therapy in patients with hepatocellular carcinoma Gyu Sang Yoo, Jeong Il Yu, Hee Chul Park International Journal of Gastrointestinal Intervention.2021; 10(4): 175. CrossRef
Antigen-Capturing Mesoporous Silica Nanoparticles Enhance the Radiation-Induced Abscopal Effect in Murine Hepatocellular Carcinoma Hepa1-6 Models Kyungmi Yang, Changhoon Choi, Hayeong Cho, Won-Gyun Ahn, Shin-Yeong Kim, Sung-Won Shin, Yeeun Kim, Taekyu Jang, Nohyun Lee, Hee Chul Park Pharmaceutics.2021; 13(11): 1811. CrossRef
First
Prev
