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Ri‐Yao Yang, Linlin Sun, Ching-Fei Li, Yu-Han Wang, Jun Yao, Hui Li, Meisi Yan, Wei‐Chao Chang, Jung-Mao Hsu, Jong‐Ho Cha and 7 more
The two T cell inhibitory receptors PD-1 and TIM-3 are co-expressed during exhausted T cell differentiation, and recent evidence suggests that their crosstalk regulates T cell exhaustion and immunotherapy efficacy; however, the molecular mechanism is unclear. Here we show that PD-1 contributes to the persistence of PD-1 + TIM-3 + T cells by binding to the TIM-3 ligand galectin-9 (Gal-9) and attenuates Gal-9/TIM-3-induced cell death. Anti-Gal-9 therapy selectively expands intratumoral TIM-3 + cytotoxic CD8 T cells and immunosuppressive regulatory T cells (T reg cells). The combination of anti-Gal-9 and an agonistic antibody to the co-stimulatory receptor GITR (glucocorticoid-induced tumor necrosis factor receptor-related protein) that depletes T reg cells induces synergistic antitumor activity. Gal-9 expression and secretion are promoted by interferon β and γ, and high Gal-9 expression correlates with poor prognosis in multiple human cancers. Our work uncovers a function for PD-1 in exhausted T cell survival and suggests Gal-9 as a promising target for immunotherapy.
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Yang, R., Sun, L., Li, C.-F., Wang, Y.-H., Yao, J., Li, H., Yan, M., Chang, W., Hsu, J.-M., Cha, J., Hsu, J. L., Chou, C.-W., Sun, X. W., Deng, Y., Chou, C., Yu, D., & Hung, M. (2021). Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy. Nature Communications, 12(1), 832. https://doi.org/10.1038/s41467-021-21099-2
Yang, Ri‐Yao, et al. "Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy." Nature Communications, vol. 12, no. 1, 2021, pp. 832, https://doi.org/10.1038/s41467-021-21099-2.
Yang, Ri‐Yao, Linlin Sun, Ching-Fei Li, Yu-Han Wang, Jun Yao, Hui Li, Meisi Yan, et al. "Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy." Nature Communications 12, no. 1 (2021): 832. https://doi.org/10.1038/s41467-021-21099-2.
Yang R., Sun L., Li C.-F. [и др.] Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy // Nature Communications. — 2021. — Vol. 12, № 1. — P. 832. — URL: https://doi.org/10.1038/s41467-021-21099-2
@article{yang2021galectin,
title = {{Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy}},
author = {Ri‐Yao Yang and Linlin Sun and Ching-Fei Li and Yu-Han Wang and Jun Yao and Hui Li and Meisi Yan and Wei‐Chao Chang and Jung-Mao Hsu and Jong‐Ho Cha and Jennifer L. Hsu and Cheng-Wei Chou and Xian Wen Sun and Yalan Deng and Chao‐Kai Chou and Dihua Yu and Mien‐Chie Hung},
journal = {Nature Communications},
year = {2021},
volume = {12},
number = {1},
pages = {832},
doi = {10.1038/s41467-021-21099-2},
url = {https://doi.org/10.1038/s41467-021-21099-2}
}TY - JOUR AU - Yang, Ri‐Yao AU - Sun, Linlin AU - Li, Ching-Fei AU - Wang, Yu-Han AU - Yao, Jun AU - Li, Hui AU - Yan, Meisi AU - Chang, Wei‐Chao AU - Hsu, Jung-Mao AU - Cha, Jong‐Ho AU - Hsu, Jennifer L. AU - Chou, Cheng-Wei AU - Sun, Xian Wen AU - Deng, Yalan AU - Chou, Chao‐Kai AU - Yu, Dihua AU - Hung, Mien‐Chie TI - Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy JO - Nature Communications VL - 12 IS - 1 SP - 832 PY - 2021 DA - 2021/02/05 DO - 10.1038/s41467-021-21099-2 UR - https://doi.org/10.1038/s41467-021-21099-2 ER -
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