T lymphocytes in hepatocellular carcinoma immune microenvironment: insights into human immunology and immunotherapy

Abstract

Hepatocellular carcinoma (HCC) is characterized by poor outcome and shows limited drug-response in clinical trials. Tumor immune microenvironment (TIME) exerts a strong selection pressure on HCC, leading to HCC evolvement and recurrence after multiple therapies. T cell-mediated immunoreaction during cancer surveillance and clearance is central in cancer immunity. Heterogenous T cell subsets play multiple roles in HCC development and progression. The re-educated T cells in TIME usually lead to deteriorated T cell response and tumor progression. Investigation into immune system dysregulation during HCC development will shed light on how to turn immune suppressive state to immune activation and induce more efficient immune response. Emerging T cell-based treatment such as cancer vaccines, CAR-T cell therapy, adoptive cell therapy, and immune checkpoint inhibitors (ICIs), have been proved to cause tumor regression in some clinical and preclinical trials. In this review, we focused on recent studies that explored T cells involved in HCC and how they affect the course of disease. We also briefly outlined current T cell-based immunotherapies in HCC.

Keywords: Hepatocellular carcinoma; T lymphocytes; immunotherapy; prognosis; tumor immune microenvironment.

Figure 1

Immune balance conditioning in HCC. The activation and suppression of immunity are associated with anti-tumor response or tumor progression. The balance of immune status is regulated by immune cells, cytokines, and immune-related receptors and ligands. TAAs: tumor associated antigens; TILs: tumor infiltrating lymphocytes; CTLs: cytotoxic lymphocytes; DC: dendritic cell; TNF- α: tumor necrosis factor α; IFN-γ: interferon γ; OX-40R: OX-40 receptor; Treg: T regulatory cell; Th7: T helper 17 cells; MDSCs: myeloid-derived suppressor cells; NKTs: natural killer T cells; TAMs: tumor-associated macrophages TGF-β: transforming growth factor-β; GITR: glucocorticoid induced TNF receptor; CAFs: cancer-associated fibroblasts.