提吉特
癌症研究
受体
生物
免疫疗法
细胞生物学
免疫学
免疫系统
生物化学
作者
Kyle B. Lupo,Sandra Torregrosa-Allen,Bennett D. Elzey,Sagar M. Utturkar,Nadia A. Lanman,Aaron Cohen-Gadol,Veronika Slivova,Mark A. McIntosh,Karen E. Pollok,Sandro Matosevic
出处
期刊:iScience
[Elsevier]
日期:2023-12-01
卷期号:26 (12): 108353-108353
标识
DOI:10.1016/j.isci.2023.108353
摘要
TIGIT is a receptor on human natural killer (NK) cells. Here, we report that TIGIT does not spontaneously induce inhibition of NK cells in glioblastoma (GBM), but rather acts as a decoy-like receptor, by usurping binding partners and regulating expression of NK activating ligands and receptors. Our data show that in GBM patients, one of the underpinnings of unresponsiveness to TIGIT blockade is that by targeting TIGIT, NK cells do not lose an inhibitory signal, but gains the potential for new interactions with other, shared, TIGIT ligands. Therefore, TIGIT does not define NK cell dysfunction in GBM. Further, in GBM, TIGIT+ NK cells are hyperfunctional. In addition, we discovered that 4-1BB correlates with TIGIT expression, the agonism of which contributes to TIGIT immunotherapy. Overall, our data suggest that in GBM, TIGIT acts as a regulator of a complex network, and provide new clues about its use as an immunotherapeutic target.
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