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

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.

• Authors: Yu Ping, Jiqi Shan, Yaqing Liu, Fengsen Liu, Liuya Wang, Zhangnan Liu, Jieyao Li, Dongli Yue, Liping Wang, Xinfeng Chen, Yi Zhang
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 72 Issue 4 Pg. 1015-1027 (Apr 2023) ISSN: 1432-0851 [Electronic] Germany
• PMID: 36261540 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Chemical References

• Programmed Cell Death 1 Receptor
• Taurine
• Antineoplastic Agents
• Cytokines
• Antibodies, Monoclonal
• Amino Acids

Topics

• Animals
• Mice
• CD8-Positive T-Lymphocytes
• Programmed Cell Death 1 Receptor
• Taurine (pharmacology, metabolism)
• Antineoplastic Agents (pharmacology)
• Cytokines (metabolism)
• Antibodies, Monoclonal (pharmacology)
• Disease Models, Animal
• Lung Neoplasms (drug therapy, metabolism)
• Amino Acids (metabolism, pharmacology)
• Tumor Microenvironment