Myeloid cells in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is highly associated with inflammation. Myeloid cells, including tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), are abundant in HCC microenvironment and are often associated with poor prognosis. Myeloid cells in HCC play a vital role in supporting tumor initiation, progression, angiogenesis, metastasis and therapeutic resistance. Here, we summarize our current knowledge about myeloid cells in HCC, and focus on their immune suppressive activities and tumor promoting functions, as well as the relevance to potential new therapies in HCC.

The Role of Cancer-Associated Fibroblasts and Fibrosis in Liver Cancer

“…TAMs appear to promote hepatocarcinogenesis through multiple mechanisms; in addition to being well established in the promotion of liver fibrosis (66, 69, 99, 100). These multiple mechanisms include several fibrosis-independent mechanisms: (a) TAMs release growth factors, cytokines, chemokines, and matrix metalloproteinases (MMPs), contributing to parenchymal cell transformation, tumor growth, ECM remodeling, angiogenesis, invasion, and metastasis (reviewed in 56); and (b) TAMs suppress antitumor immunity through the recruitment of regulatory T cells (Tregs) and increased expression of inhibitors of tumor-specific T cell immunity, such as PD-L1 (97), galectin 9 (101), IL-10, CCL17, and CCL22 (reviewed in 102). …”

Host antitumor resistance improved by the macrophage polarization in a chimera model of patients with HCC

“…26 However, once tumors are established, Mf infiltrated into the tumor tissue differentiate into TAMs (M2 phenotype), 25 which promote growth, invasion, and metastasis of tumor cells, thus inducing angiogenesis and suppressing antitumor immunity. 5,24 In our study, TAMs in tumors of group-3 HCC patients were identified as CD68 C CCL1 C cells (M2b phenotype). The higher prevalence of regulatory T cells (Tregs) has been demonstrated in the intratumor tissues of HCC patients, resulting in the suppression of host antitumor immunity.…”

“…[5][6][7] However, these cells infiltrating the HCC tissues easily become dysfunctional or functionally exhausted depending on the tumor microenvironment. 5 Functionally exhausted T cells are known to express high levels of programmed cell death 1 (PD-1) receptor. 8 PD-1 is expressed on T cells upon recognition of a target antigen via the T-cell receptor (TCR).…”

T cell immunotherapy in hepatitis B Virus related hepatocellular carcinoma

“…Major progress have been made in the development of immunotherapy approaches that attempts to rejuvenate and/or induce anti-tumour T cell responses in the HCC microenvironment, like immune checkpoint inhibitors (ICIs) [14] . However, this approach requires a pre-existing inflammatory tumour microenvironment with significant immune cell infiltration, the expression of immune checkpoints on tumour cells, and/or an existing anti-tumour immune response, in order to exert an anti-tumour effect [13,[15][16][17][18] . With the intra-and inter-HCC patient tumour heterogeneity, it would be difficult to expect the mechanism of action for the therapy to be intact for all tumour nodules, especially in metastatic nodules that develop in different anatomical environments [19] .…”