Triterpenoids of Rhus chinensis Supressed Colorectal Cancer Progress by Enhancing Antitumor Immunity and CD8 + T Cells Tumor Infiltration

Abstract

The absence of CD8+ T cells in the tumor center has become a major obstacle in the immunotherapy of colorectal cancer. Therefore, new therapeutic strategies are urgently needed to promote the accumulation of CD8+ T cells in the tumor center. Previous studies have shown that triterpenoid of Rhus chinensis (TER) is involved in the proliferation and apoptosis of colorectal cancer cells, and can regulate their immune activity, but its mechanism needs to be further elucidated. In this study, the antitumor effect and adaptive immune response of TER on tumor-bearing mice were evaluated and compared with 5-fluorouracil. The results showed that TER could significantly inhibit tumor growth and prolong the survival time of tumor-bearing mice. The In Vivo studies have shown that TER can not only enhance antitumor immunity and promote the accumulation of CD8 + T cells to tumor sites, but also inhibit tumor progression by regulating the expression of PD-1 and PD-L1 and significantly reducing the mortality of mice. Our study demonstrated for the first time that TER has oncolytic effect, and recruited adaptive immune cells to enhance the efficacy of anti-PD-1/PD-L1 in colorectal cancer, which provides a potential therapeutic target for combined immunotherapy of colorectal cancer.

Acknowledgments

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Conflict of Interests

We wish to confirm that there are no known conflicts of interest with this publication and that there is no significant financial support for this work that may affect the results.

Authors’ Contribution

Gang Wang designed experiments; Zi-Meng Li and Yang Yu carried out experiments; Zi-Meng Li prepared figures 1-4. Yang Yu analyzed experimental results and prepared figures 5-10. Zhi-Min Zhu and Zhi-Jie Wang analyzed sequencing data and developed analysis tools. Gang Wang wrote the manuscript and prepared figures 11 and Min-Fang Tao revised the manuscript.

Ethics Statements

All the animal experiments complied with the guidelines and were conducted in accordance with the care and use of laboratory animals as well as Animal Studies Committee established by the Laboratory Animal Center of Putuo Hospital, Shanghai University of Traditional Chinese Medicine. The animal housing and care guidelines were in line with the guide for the care and use of Laboratory animals Shanghai University of Traditional Chinese Medicine) of which the authors have indicated in the manuscript.

Contributor Information

Gang Wang, Email: [email protected]

Min-Fang Tao, Email: [email protected]

Data Availability Statement

All data generated or analyzed during this study are included in this article.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (No. 81673827), the Shanghai Health Development Planning Committee Chinese Medicine Research Project (No. 2016JP008) and the Shanghai Xuhui Science and Technology Committee Research Project (SHXH201640).