The DOI matches its Crossref record; 82 of the 82 references it cites were found in a registry or an index.
Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy
Open accessAbstract
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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Cites
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F.-A., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E.-M., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,845
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838
GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses
Tang, Z., Li, C., Kang, B., Gao, G., Li, C., & Zhang, Z. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx247 · Cited by 9,849
Self-citationThe immune contexture in human tumours: impact on clinical outcome
Fridman, W. H., Pagès, F., Sautès-Fridman, C., & Galon, J. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3245 · Cited by 4,981
Ishida, Y., Agata, Y., Shibahara, K., & Honjo, T. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05481.x · Cited by 3,256
Molecular mechanisms of T cell co-stimulation and co-inhibition
Chen, L., & Flies, D. B. (2013) · Nature Reviews Immunology · doi:10.1038/nri3405 · Cited by 3,114
CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition
Buchbinder, E. I., & Desai, A. (2016) · American Journal of Clinical Oncology · doi:10.1097/coc.0000000000000239 · Cited by 2,360
Miller, B. C., Sen, D. R., Al Abosy, R., Bi, K., Virkud, Y. V., LaFleur, M. W., Yates, K. B., Lako, A., Felt, K., Naik, G. S., et al. (2019) · Nature Immunology · doi:10.1038/s41590-019-0312-6 · Cited by 2,087
Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity
Sakuishi, K., Apetoh, L., Sullivan, J. M., Blazar, B. R., Kuchroo, V. K., & Anderson, A. C. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20100643 · Cited by 2,072
The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity
Zhu, C., Anderson, A. C., Schubart, A., Xiong, H., Imitola, J., Khoury, S. J., Zheng, X. X., Strom, T. B., & Kuchroo, V. K. (2005) · Nature Immunology · doi:10.1038/ni1271 · Cited by 2,057
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Immunosuppressive cells in cancer: mechanisms and potential therapeutic targets
Tie, Y., Tang, F., Wei, Y.-Q., & Wei, X.-W. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01282-8 · Cited by 591
Luo, H., Xia, X., Huang, L.-B., An, H., Cao, M., Kim, G. D., Chen, H.-N., Zhang, W.-H., Shu, Y., Kong, X., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-34395-2 · Cited by 567
Self-citationGamma delta T-cell-based immune checkpoint therapy: attractive candidate for antitumor treatment
Gao, Z., Bai, Y., Lin, A., Jiang, A., Zhou, C., Cheng, Q., Liu, Z., Chen, X., Zhang, J., & Luo, P. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01722-0 · Cited by 138
Gerace, D., Zhou, Q., Kenty, J. H.-R., Veres, A., Sintov, E., Wang, X., Boulanger, K. R., Li, H., & Melton, D. A. (2023) · Cell Reports Medicine · doi:10.1016/j.xcrm.2022.100879 · Cited by 88
Self-citation
Metadata
- Authors
- Yang, R., Sun, L., Li, C.-F., Wang, Y.-H., Yao, J., Li, H., Yan, M., Chang, W.-C., Hsu, J.-M., Cha, J.-H., Hsu, J. L., Chou, C.-W., Sun, X., Deng, Y., Chou, C.-K., Yu, D., & Hung, M.-C.
- Venue
- Nature Communications
- Published
- 2021-02-05
- Volume
- 12
- Issue
- 1
- Pages
- 832-832
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W3128803455
- Cited by
- 632
- References
- 82
- FWCI
- 28.34
- Type
- journal article
- Language
- en
- Open access
- gold
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- CoChat. (2026). Citation check: Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy. https://app.cochat.ai/papers/10.1038/s41467-021-21099-2
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- Yang, R., Sun, L., Li, C.-F., Wang, Y.-H., Yao, J., Li, H., Yan, M., Chang, W.-C., Hsu, J.-M., Cha, J.-H., Hsu, J. L., Chou, C.-W., Sun, X., Deng, Y., Chou, C.-K., Yu, D., & Hung, M.-C. (2021). Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy. Nature Communications. https://doi.org/10.1038/s41467-021-21099-2
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
