TIGIT presents earlier expression dynamic than PD-1 in activated CD8(+) T cells and is upregulated in non-small cell lung cancer patients

Lung Cancer
06/09/2020

Exp Cell Res. 2020 Sep 2:112260. doi: 10.1016/j.yexcr.2020.112260. Online ahead of print.

ABSTRACT

CD8+ T cells are considered a critical component of antitumor immunity. However, tumor-infiltrating CD8+ T cells may express more than one checkpoint molecules that have the potential to inhibit effector responses alone or cooperatively. Here, we focused on the expression dynamic of TIGIT and PD-1 in CD8+ T cells. TIGIT+ subset presented significantly higher PD-1 expression than TIGIT- subset in circulating CD8+ T cells. The expression dynamic of TIGIT and PD-1 was then tracked. In total CD8+ T cells, TIGIT mRNA increased more rapidly than PD-1 mRNA, and TIGIT+ CD8+ T cells upregulated PD-1 more rapidly than TIGIT- CD8+ T cells. Next, 24-h-stimulated CD8+ T cells were re-sorted into TIGIT+ and TIGIT- subsets, and the TIGIT+ cells that came from TIGIT- cells also presented significantly more rapid PD-1 induction than persistent TIGIT- CD8+ T cells. In non-small cell lung cancer (NSCLC) patients, the expression of PD-1 was more enriched in TIGIT+ cells than in TIGIT- cells in both circulating CD8+ T cells and tumor-infiltrating CD8+ T cells. Function analysis revealed that TIGIT+ CD8 T cells presented lower interferon-gamma, perforin 1, and granzyme B upregulation than TIGIT- CD8 T cells, especially in NSCLC patients. Overall, these data indicated that TIGIT presented earlier expression dynamic than PD-1 in activated CD8+ T cells and was upregulated in NSCLC patients.