# Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy

“Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy” (2021), by Ri‐Yao Yang et al. Immunology and Microbiology research paper. Original abstract below, unchanged. A free PDF is available.

- Authors: 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 et al.
- Published: February 5, 2021
- Field: Immunology and Microbiology
- DOI: https://doi.org/10.1038/s41467-021-21099-2
- Free PDF: https://www.nature.com/articles/s41467-021-21099-2.pdf

## Abstract

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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