γδ T cells in hepatocellular carcinoma patients present cytotoxic activity but are reduced in potency due to IL-2 and IL-21 pathways

International Immunopharmacology
Hang JiangQinghua Shao

Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver carcinoma and has one of the highest mortality rates of all cancers. The γδ T cells could infiltrate HCC and have demonstrated potent tumor-killing capacity. Here, we found that in peripheral blood, the vast majority of γδ T cells were Vδ2 T cells. In HCC patients, the frequency of Vδ2 T cells was significantly lower than in controls. γδ T cells that were harvested directly ex vivo possessed very limited capacity to eliminate Zol-loaded HCC cell lines, even at a high effector to target ratio. In vitro expansion with Zol could significantly increase the capacity of γδ T cells to eliminate HCC cell lines. But even with in vitro expansion, the γδ T cells from HCC patients presented significantly lower cytotoxic capacity than the γδ T cells from healthy individuals. The expression of IL-2 and IL-21 by γδ T cells was significantly lower in HCC patients than in control volunteers. Supplementing recombinant human IL-2 and IL-21 in the in vitro expansion culture increased the cytotoxic capacity of γδ T cells. In addition, the frequency of PD-1+ γδ T cells was significantly higher in HCC patients than in controls ex vivo, and was significantly elevated after in vitro expans...Continue Reading

Citations

Oct 13, 2020·Cellular & Molecular Immunology·Yongyan Chen, Zhigang Tian
Mar 6, 2021·Frontiers in Immunology·Yang LiXi Chen

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