Immune landscape of hepatocellular carcinoma microenvironment: Implications for prognosis and therapeutic applications

Abstract

The development of immunotherapy for solid tumours has boosted interest in the contexture of tumour immune microenvironment (TIME). Several lines of evidence indicate that the interplay between tumour cells and TIME components is a key factor for the evolution of hepatocellular carcinoma (HCC) and for the likelihood of response to immunotherapeutics. The availability of high‐resolution methods will be instrumental for a better definition of the complexity and diversity of TIME with the aim of predicting disease outcome, treatment response and possibly new therapeutic targets. Here, we review current knowledge about the immunological mechanisms involved in shaping the clinical course of HCC. Effector cells, regulatory cells and soluble mediators are discussed for their role defining TIME and as targets for immune modulation, together with possible immune signatures for optimization of immunotherapeutic strategies.

A Single‐Cell Perspective of the Mammalian Liver in Health and Disease

“…Altered immune landscape is a feature of tumor microenvironment associated with liver cancer . Several immune cell types including regulatory T cells (Tregs), exhausted CD8 + effector T cells, tumor‐associated macrophages, and myeloid‐derived suppressor cells have been shown to accumulate in the hepatocellular carcinoma (HCC) microenvironment .…”

“…Altered immune landscape is a feature of tumor microenvironment associated with liver cancer. (25) Several immune cell types including regulatory T cells (Tregs), exhausted CD8 + effector T cells, tumor-associated macrophages, and myeloid-derived suppressor cells have been shown to accumulate in the hepatocellular carcinoma (HCC) microenvironment. (26) To better understand the mechanisms and regulatory pathways leading to T-cell exhaustion and accumulation of Tregs in liver cancer, Zheng et al performed scRNA-seq on sorted T cells from peripheral blood, normal liver tissue adjacent to tumor, and tumor tissues from 6 patients with HCC.…”

Tumor-infiltrating immune cells in hepatocellular carcinoma: Tregs is correlated with poor overall survival

“…The HCC immune feature, due to the chronic inflammation and cirrhosis in most HCC patients, is complicated and varies dynamically [8,9]. The heterogeneity of the HCC ecosystem influences the growth, invasion, and metastasis of tumor and efficacy of treatment [4].…”

Natural Killer Cell Responses in Hepatocellular Carcinoma: Implications for Novel Immunotherapeutic Approaches

“…Moreover, the physical status of the HCC microenvironment, including characteristics such as hypoxia and the production of metabolites by the tumor cells may also impair NK cell function. For example, lactate, adenosine, indoleamine 2,3-dioxygenase can interfere with NK cell activation and phenotype [28][29][30].…”