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.

Keywords: Antitumor immunity; CD8+ T cell; Calcium signaling; MAPK signaling; PD-1 blockade antibody; Taurine.