Immune Regulatory Networks and Therapy of γδ T Cells in Liver Cancer: Recent Trends and Advancements

Abstract

The roles of γδ T cells in liver cancer, especially in the potential function of immunotherapy due to their direct cytotoxic effects on tumor cells and secretion of important cytokines and chemokines, have aroused research interest. This review briefly describes the basic characteristics of γδ T cells, focusing on their diverse effects on liver cancer. In particular, different subtypes of γδ T cells have diverse or even opposite effects on liver cancer. We provide a detailed description of the immune regulatory network of γδ T cells in liver cancer from two aspects: immune components and nonimmune components. The interactions between various components in this immune regulatory network are dynamic and pluralistic, ultimately determining the biological effects of γδ T cells in liver cancer. We also integrate the current knowledge of γδ T-cell immunotherapy for liver cancer treatment, emphasizing the potential of these cells in liver cancer immunotherapy.

Keywords: Immunotherapy; Liver cancer; Tumor microenvironment; γδ T cells.

Fig. 1. The subtypes of γδ T cells and the pathophysiological roles of γδ T cells in tumors.

Human γδ T cells are usually divided into Vδ1+, Vδ2+, and Vδ3+γδ T cells according to the arrangement of the γ chain and δ chain. Vδ1+ γδ T cells and Vδ2+ γδ T cells can be further classified by the expression of the memory markers CD45RA and CD27. The pathophysiological roles of γδ T cells include their cytotoxic activity against target cells, the secretion of different types of cytokines and chemokines and their interaction with other cells, such as αβ T cells, dendritic cells (DCs), B cells, natural killer cells (NKs), and macrophages. DCs, dendritic cells; NKs, natural killer cells. IFN-γ, interferon γ; CCR, C-C chemokine receptor; TNF-α, tumor necrosis factor-α; IL, interleukin; TCR, T cell receptor.

Fig. 2. A dual role of γδ T cells in liver cancer.

Different subtypes of γδ T cells have diverse or even opposite effects on liver cancer. IFN-γ, interferon γ; TGF-β, tumor growth factor-β; TNF-α, tumor necrosis factor-α; IL, interleukin; LAG3, lymphocyte activation gene-3; PD-1, programmed death -1; CD96, cluster of differentiation-96; ULBP1, ul16-binding protein; NKGD2, natural killer group member D.

Fig. 3. Brief summary of immune regulatory networks of γδ T cells involved in the microenvironment of liver cancer.

The immune regulatory network of γδ T cells in liver cancer is extremely sophisticated and multivariant. Immune regulatory networks of γδ T cells are involved in the immune microenvironment of liver cancer through immune molecules, immune cells and nonimmune components. CD, cluster of differentiation; NK cell, natural-killer cell; MDSC, Myeloid-derived suppressor cell; Treg cell, T regulatory cell; CCR, C-C chemokine receptor; IL, interleukin; IFN-γ, interferon γ; TNF-α, tumor necrosis factor-α.