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Combination therapy with anti-T-cell immunoglobulin and mucin-domain containing molecule 3 and radiation improves antitumor efficacy in murine hepatocellular carcinoma

Authors
 Kyoung-Jin Kim  ;  Hye Won Lee  ;  Jinsil Seong 
Citation
 JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Vol.36(5) : 1357-1365, 2021-05 
Journal Title
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
ISSN
 0815-9319 
Issue Date
2021-05
Keywords
Antitumor effect ; Combination therapy ; Hepatocellular carcinoma ; Immune checkpoint inhibitor ; Radiation
Abstract
Background and aim: T-cell immunoglobulin and mucin-domain containing molecule 3 (TIM3) has emerged as a promising immune checkpoint inhibitor target; however, immune checkpoint inhibitor monotherapy does not benefit a substantial percentage of patients. Therefore, this study investigated the antitumor effect of anti-TIM3 therapy combined with radiation in a murine hepatocellular carcinoma (HCC) model.

Methods: The effect of radiation on TIM3 expression was determined in murine and human HCC cells using western blotting, immunohistochemistry, and flow cytometry. Tumor growth and survival rate were measured to evaluate the antitumor effect of this combination therapy. Tumor immunological parameters were assessed using flow cytometry and histology.

Results: TIM3 was upregulated in tumor-infiltrating CD8+ and CD4+ T cells in radiation-treated HCa-1-implanted mice. Combination treatment significantly delayed tumor growth compared with monotherapy (P < 0.01). Overall survival was improved in the combination group compared with that in the anti-TIM3 or radiation monotherapy groups (median survival time: 52 days vs 26 or 38 days, respectively, P < 0.001). The antitumor effect of the combination treatment was associated with increased apoptosis and decreased proliferation of tumor cells and reinvigorated CD8+ T-cell activation. CD8+ T-cell depletion reversed the antitumor efficacy of the combination treatment. These findings suggest that CD8+ T cells play key roles in the therapeutic effect of the combination treatment.

Conclusion: Anti-TIM3 and radiation combination therapy significantly improved the antitumor effect in a murine HCC model, as evidenced by inhibited tumor growth and increased overall survival. This approach could be a novel combined immune-radiotherapy strategy for HCC.
Full Text
https://onlinelibrary.wiley.com/doi/10.1111/jgh.15319
DOI
10.1111/jgh.15319
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Seong, Jin Sil(성진실) ORCID logo https://orcid.org/0000-0003-1794-5951
Lee, Hye Won(이혜원) ORCID logo https://orcid.org/0000-0002-3552-3560
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/184300
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