Stereotactic body radiation therapy (SBRT) increases anti-PD-1 antitumor activity by enhancing the tumor immune microenvironment in mice with metastatic hepatocellular carcinoma

Background To explore the effect of radiotherapy on anti-pd-1 anti-tumor activity in metastatic hepatocellular carcinoma. Methods Patients with metastatic HCC treated with intensity-modulated radiation therapy (IMRT) in combination with immunotherapy ( n  = 13) were retrospectively analyzed by compa...

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Vydané v:Discover. Oncology Ročník 16; číslo 1; s. 1081 - 19
Hlavní autori: Xu, Ke, Gu, Tao, Su, Ke, Liu, Xin, He, Bingsheng, He, Jie, Chi, Hao, Zhou, Xuancheng, Liu, Hanlin, Xiao, Rui, Tang, Xue, Ye, Qinni, Zhou, Xue, Liu, Yingpeng, Xiong, Jie, Wang, Pan, Li, Han, He, Kun, Guo, Lu, Han, Yunwei
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: New York Springer US 13.06.2025
Springer Nature B.V
Springer
Predmet:
Antibodies
Biotechnology
Cancer Research
Cancer therapies
Cell culture
Disease
Ethics
Fatalities
FDA approval
Hepatitis
Hospitals
Hypoxia
Immune system
Immunotherapy
Internal Medicine
Liver cancer
Liver cirrhosis
Lymphocytes
Medical research
Medicine
Medicine & Public Health
Metastasis
Metastatic hepatocellular carcinoma
Molecular Medicine
Oncology
PD-1 antibody
Penicillin
Radiation therapy
Radiotherapy
Stereotactic body radiation therapy
Surgical Oncology
Toxic effects
Transplants & implants
Tumor immune microenvironment
Tumors
Viral infections
United States > US
China
Tumor immune microenvironment
Stereotactic body radiation therapy
Toxic effects
PD-1 antibody
Immunotherapy
Metastatic hepatocellular carcinoma
ISSN:2730-6011, 2730-6011
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Shrnutí:Background To explore the effect of radiotherapy on anti-pd-1 anti-tumor activity in metastatic hepatocellular carcinoma. Methods Patients with metastatic HCC treated with intensity-modulated radiation therapy (IMRT) in combination with immunotherapy ( n  = 13) were retrospectively analyzed by comparing its efficacy with that of immunotherapy alone ( n  = 12) as well as untreated ( n  = 20) patients with metastatic hepatocellular carcinoma. Animal experiment used mouse hepatocellular carcinoma H22 cell metastatic tumor model and were also divided into a control group, a PD-1 antibody group, an SBRT group, and an SBRT combined with a PD-1 antibody group. SBRT treatment is 8 Gy×3 F. The growth curves of body weight, irradiated tumor (the primary tumor), and non-irradiated tumor (secondary tumor) were plotted for each group of tumor-bearing mice. For this study, we used flow cytometry to examine effector CD8 + T cells expression in both irradiated and non-irradiated tumors, the CD4 + T and CD4+/CD8 + T cells ratio in the spleen, and used enzyme-linked immunosorbent assays (ELISA) to analyze the concentrations of IFN-γ and IL-10 in serum. Tumors were additionally stained with immunohistochemistry Ki-67 and TdT-mediated dUTP nick end labeling (TUNEL). We used hematoxylin-eosin (HE) staining of liver, spleen, lungs, kidneys, and heart to assess the anti-tumor activity of each group of tumor-bearing mice and their tolerance to determine the safety of the approach. Results Clinical results: The median survival of IMRT + PD-1 group, PD-1 group, and control group were 17.5 months (95Confidence Interval (CI) 13.2–21.8), 12.5 months (95CI 9.0–16.0), and 5.2 months (95CI 5.5–12.9), respectively ( P  < 0.001). SBRT combined with PD-1 antibody improved tumor control in both radiated and non-radiated tumors, resulting in a complete cure of the half of mice in animal studies. This was linked to an increased in CD8 + effector T cells infiltration triggered by radiotherapy. HE staining of mice in the SBRT combined with the PD-1 treatment group suggested no damage to the liver, spleen, lungs, kidneys, and heart. Conclusions This study showed that SBRT, while being well-tolerated, significantly increased anti-PD-1 antitumor activity by enhancing the tumor immune microenvironment in mice with metastatic hepatocellular carcinoma without significant toxic side effects. Disclaimer : This manuscript was previously submitted as a preprint only in Experimental Hematology & Oncology and has no conflict of interest with this submission.
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SourceType-Scholarly Journals-1
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ISSN:2730-6011
2730-6011
DOI:10.1007/s12672-025-02914-4