Tim-3 suppresses the killing effect of Vγ9Vδ2 T cells on colon cancer cells by reducing perforin and granzyme B expression.

Abstract:

:Gamma delta (γδ) T cell-based tumor immunotherapy has been one of the most promising cancer immunotherapeutic strategies. However, the key regulators of the Vγ9Vδ2 T cell-mediated antitumor response remain unclear. Recently, mounting reports have indicated that Tim-3 performs critical roles in the regulation of the activities of immune cells, including Vγ9Vδ2 T cells. However, the roles of Tim-3 in Vγ9Vδ2 T cell-mediated killing of colon cancer cells and the underlying mechanism remain largely unknown. Here, the proportion of Tim-3+ γδ T cells was significantly increased in both the peripheral blood and colon cancer tissue of patients and was significantly associated with TNM staging and tumor volume. Additionally, the activation of Tim-3 signaling significantly inhibited the killing efficiency of Vγ9Vδ2 T cells against colon cancer cells. In addition, Tim-3 signaling reduced the expression of perforin and granzyme B in Vγ9Vδ2 T cells. Blocking the perforin/granzyme B pathway also decreased the cytotoxicity of Vγ9Vδ2 T cells to colon cancer cells. Moreover, Tim-3 signaling reduced the perforin and granzyme B expression of Vγ9Vδ2 T cells in an ERK1/2 signaling pathway-dependent manner. This knowledge reveals that Tim-3 may be a promising therapeutic target to improve Vγ9Vδ2 T cell-based adoptive immunotherapy for colon cancer.

journal_name

Exp Cell Res

authors

Li X,Lu H,Gu Y,Zhang X,Zhang G,Shi T,Chen W

doi

10.1016/j.yexcr.2019.111719

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

111719

issue

1

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(19)30598-1

journal_volume

386

pub_type

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