Tim-3 suppresses the killing effect of V γ9Vδ2 T cells on colon cancer cells by reducing perforin and granzyme B expression.

Tim-3 suppresses the killing effect of Vγ9Vδ2 T cells on colon cancer cells by reducing perforin and granzyme B expression. Exp Cell Res. 2019 Nov 11;:111719 Authors: Li X, Lu H, Gu Y, Zhang X, Zhang G, Shi T, Chen W 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...
Source: Experimental Cell Research - Category: Cytology Authors: Tags: Exp Cell Res Source Type: research