[HTML][HTML] TIGIT predominantly regulates the immune response via regulatory T cells

S Kurtulus, K Sakuishi, SF Ngiow… - The Journal of …, 2015 - Am Soc Clin Investig
S Kurtulus, K Sakuishi, SF Ngiow, N Joller, DJ Tan, MWL Teng, MJ Smyth, VK Kuchroo
The Journal of clinical investigation, 2015Am Soc Clin Investig
Coinhibitory receptors are critical for the maintenance of immune homeostasis. Upregulation
of these receptors on effector T cells terminates T cell responses, while their expression on
Tregs promotes their suppressor function. Understanding the function of coinhibitory
receptors in effector T cells and Tregs is crucial, as therapies that target coinhibitory
receptors are currently at the forefront of treatment strategies for cancer and other chronic
diseases. T cell Ig and ITIM domain (TIGIT) is a recently identified coinhibitory receptor that …
Coinhibitory receptors are critical for the maintenance of immune homeostasis. Upregulation of these receptors on effector T cells terminates T cell responses, while their expression on Tregs promotes their suppressor function. Understanding the function of coinhibitory receptors in effector T cells and Tregs is crucial, as therapies that target coinhibitory receptors are currently at the forefront of treatment strategies for cancer and other chronic diseases. T cell Ig and ITIM domain (TIGIT) is a recently identified coinhibitory receptor that is found on the surface of a variety of lymphoid cells, and its role in immune regulation is just beginning to be elucidated. We examined TIGIT-mediated immune regulation in different murine cancer models and determined that TIGIT marks the most dysfunctional subset of CD8+ T cells in tumor tissue as well as tumor-tissue Tregs with a highly active and suppressive phenotype. We demonstrated that TIGIT signaling in Tregs directs their phenotype and that TIGIT primarily suppresses antitumor immunity via Tregs and not CD8+ T cells. Moreover, TIGIT+ Tregs upregulated expression of the coinhibitory receptor TIM-3 in tumor tissue, and TIM-3 and TIGIT synergized to suppress antitumor immune responses. Our findings provide mechanistic insight into how TIGIT regulates immune responses in chronic disease settings.
The Journal of Clinical Investigation