TIGIT contributes to the regulation of 4-1BB and does not define NK cell dysfunction in glioblastoma
Recommended Citation
Lupo, Kyle B.; Torregrosa-Allen, Sandra; Elzey, Bennett D.; Utturkar, Sagar; Lanman, Nadia A.; Cohen-Gadol, Aaron A.; Silvova, Veronika; McIntosh, MacKenzie; Pollok, Karen E.; and Matosevic, Sandro, "TIGIT contributes to the regulation of 4-1BB and does not define NK cell dysfunction in glioblastoma" (2023). Purdue University Libraries Open Access Publishing Fund. Paper 183.
http://dx.doi.org/10.1016/j.isci.2023.108353
DOI
10.1016/j.isci.2023.108353
Date of this Version
10-26-2023
Keywords
Health sciences, Biological sciences, Immunology, Cancer
Abstract
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.
Comments
This is the publisher PDF of Lupo et al., iScience 26, 108353 December 15, 2023. This article is distributed under a CC-BY-NC-ND license, and is available at DOI: 10.1016/j.isci.2023.108353.