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Taurine enhances the antitumor efficacy of PD-1 antibody by boosting CD8+ T cell function

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Abstract

The functional state of CD8+ T cells determines the therapeutic efficacy of PD-1 blockade antibodies in tumors. Amino acids are key nutrients for maintaining T cell antitumor immunity. In this study, we used samples from lung cancer patients treated with PD-1 blockade antibodies to assay the amino acids in their serum by mass spectrometry. We found that lung cancer patients with high serum taurine levels generally responded to PD-1 blockade antibody therapy, in parallel with the secretion of high levels of cytotoxic cytokines (IFN-γ and TNF-α). CD8+ T cells cultured with exogenous taurine exhibited decreased apoptosis, enhanced proliferation, and increased secretion of cytotoxic cytokines. High SLC6A6 expression in CD8+ T cells was positively associated with an effector T cell signature. SLC6A6 knockdown limited the function and proliferation of CD8+ T cells. RNA sequencing revealed that SLC6A6 knockdown altered the calcium signaling pathway, oxidative phosphorylation, and T cell receptor signaling in CD8+ T cells. Furthermore, taurine enhanced T cell proliferation and function in vitro by stimulation of PLCγ1-mediated calcium and MAPK signaling. Taurine plus immune checkpoint blockade antibody significantly attenuated tumor growth and markedly improved the function and proliferation of CD8+ T cells in a mouse tumor model. Thus, our findings indicate that taurine is an important driver for improving CD8+ T cell immune responses and could serve as a potential therapeutic agent for cancer patients.

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Data availability

The datasets in current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank Henan Key Laboratory for Pharmacology of Liver Diseases for assistance with animal experiments.

Funding

This work was supported by the National Natural Science Foundation of China (Grant nos. 82102869, 81872333 and 91942314), Medical Science and Technology Project of Henan Province (Grant no. SBGJ202103083), China Postdoctoral Science Foundation (Grant no. 2021M692928), and Excellent Youth Project for Health talents in Henan Province (Grant No. YXKC2020052).

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Authors and Affiliations

  1. Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

    Yu Ping, Jiqi Shan, Yaqing Liu, Fengsen Liu, Liuya Wang, Zhangnan Liu, Xinfeng Chen & Yi Zhang

  2. Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

    Jieyao Li, Dongli Yue & Liping Wang

  3. State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, Henan, China

    Yi Zhang

  4. School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China

    Yi Zhang

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  1. Yu Ping
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Contributions

All authors contributed to the study conception and design. This study was designed and supervised by YZ and YP. Data collection and analysis were performed by YP, JS, FL, LW and ZL. Material preparation was performed by YL, JL, DY and LW. The first draft of the manuscript was written by YP. The manuscript was edited by XC and YZ. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Yi Zhang.

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The authors declare no competing interests.

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The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

This study was approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (2021-KY-1105–002).

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Informed consent was obtained from all individual participants included in the study.

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All animal experiments were approved by the Animal Care and Ethics Committee of the First Affiliated Hospital of Zhengzhou University.

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Ping, Y., Shan, J., Liu, Y. et al. Taurine enhances the antitumor efficacy of PD-1 antibody by boosting CD8+ T cell function. Cancer Immunol Immunother 72, 1015–1027 (2023). https://doi.org/10.1007/s00262-022-03308-z

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