CD155/TIGIT signaling regulates the effector function of tumor-infiltrating CD8+ T cell by NF-κB pathway in colorectal cancer.

Abstract

BACKGROUND AND AIM:

CD155/T-cell immunoglobulin and ITIM domain (TIGIT) suppressed anti-cancer immunity in several cancers, but its roles in colorectal cancer (CRC) were not clear. Here, we investigated its roles in CRC.

METHODS:

The percentages of CD8+ T cells expressing TIGIT and secreting cytokines (IL-2, TNF-α, and IFNγ) were evaluated by flow cytometry. The expression level of CD155 was determined by western blot and immunohistochemistry. The levels of cytokines were determined by enzyme-linked immunosorbent assay. The activation of the nuclear factor-kappa B (NF-κB) pathway was examined by western blot and immunofluorescent assay.

RESULTS:

T-cell immunoglobulin and ITIM domain was overexpressed on CD8+ T cells of CRC patients and mice. CD155 was overexpressed in mice CRC tissues and cells. The addition of CD155 recombinant protein could decrease the percentages of CD8+ T cells secreting cytokines. Blocking TIGIT could increase the percentages of cytokine-secreting CD8+ T cells. Coculturing with CD155-knockdown CRC cells could upregulate the percentages of CD8+ T cells secreting cytokines. Blocking TIGIT partially counteracted the effect of the knockdown of CD155. Besides, coculturing with CD155-knockdown CRC cells could promote the secretion of cytokines, activate the NF-κB pathway, and enhance the nuclear translocation of p65. And these effects were counteracted by the application of an NF-κB inhibitor. Finally, blocking TIGIT played anti-cancer roles such as suppression of tumor growth, increasing the percentages of cytokine-secreting CD8+ T cells and activation of the NF-κB signaling pathway.

CONCLUSION:

Suppressing CD155/TIGIT exerted anti-cancer effects against CRC, and our findings provided a potential therapeutic approach to treat CRC.

• Authors: Shanshan Li, Jihu Ding, Ying Wang, Xianling Wang, Lin Lv
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 37 Issue 1 Pg. 154-163 (Jan 2022) ISSN: 1440-1746 [Electronic] Australia
• PMID: 34734434 (Publication Type: Journal Article)
• Copyright: © 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Chemical References

• NF-kappa B
• Receptors, Immunologic
• Receptors, Virus
• TIGIT protein, human
• poliovirus receptor

Topics

• Animals
• CD8-Positive T-Lymphocytes (metabolism, pathology)
• Colorectal Neoplasms (genetics, pathology)
• Humans
• Mice
• NF-kappa B (metabolism)
• Receptors, Immunologic (genetics, metabolism)
• Receptors, Virus (genetics, metabolism)
• Signal Transduction