Table 6 List of various components of HCC tumor microenvironment and their role

1

Tumor associated macrophages (TAMs)

Tumor development by impairing cytotoxic CD8+ T cell mediated immune responses

Chemo resistance in HCC.

2

Cancer associated fibroblasts (CAFs)

Produces growth factors like hepatocyte growth factor (HGF), members of the epidermal growth factor (EGF), fibroblast growth factor (FGF) and members of Wnt families, and cytokines, such as stromal-derived factor (SDF)-1α and IL-6

Chemo resistance in HCC

[126, 127]

3

Matrix metalloproteinases (MMPs)

Causes tissue remodeling, inflammation, tumor cell growth and metastasis in many cancers. MMP-2,-9, and -14 activate TGF-β1, which reciprocally activates MMP. Upregulation of MMP-9 is connected with provocation of PI3 K/PTEN/AKT/mTOR pathways in human HCCs. MMPs also inhibit apoptosis signaling in cancer cells

Chemo resistance in HCC

[128, 129]

4

Immune cells

CD8⁺ T cells, NK cells are fooled by cancer cells as an immune evasion mechanism

Poor prognosis in HCC patients

[130, 131]

5

Kupffer cells

Upon activation secrete excessive level of osteopontin

Chemo resistance of cisplatin in small cell lung cancer. It can be postulated to play a role in Hepatocellular carcinoma too

6

Hepatic stellate cells (HSCs)

Produce collagen in the liver. They get activated upon liver damage and undergo phenotypic changes leading liver fibrosis. They secrete hepatocyte growth factor

Chemo resistance in HCC