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

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.

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