Table 2:
HSC-immune cells interaction contributing to the immunosuppressive and pro-tumorigenic environment in HCC.
| Cell Types | Mechanisms | Effects | References |
|---|---|---|---|
| Tregs | Promote Treg differentiation and survival; Treg reduces NK-mediated clearance of HSCs enhance Treg immunosuppressive activity via TGF-β and IL-10 |
Immunosuppression and persistence of activated HSCs | Chou, H. S. et al. 2011. [71] Langhans, B. et al. 2013 [72] Dunham, R. M. et al. 2013. [73] Zhao, W. et al. 2012. [74] Dangi, A. et al. 2012. [75] |
| Cytotoxic T Cells | Induce T cell apoptosis via Fas/FasL; suppress PD-L1 signaling inhibit proliferation and reduce cytotoxicity |
Reduced cytotoxicity, leading to immune evasion | Zhao, W. et al. 2012. [74] Charles, R. et al. 2013. [76] Yu, M. C. et al. 2004. [77] Xia, Y. et al. 2011. [78] Xia, Y. H. et al. 2013. [79] Dangi, A. et al. 2012. [75] Zhao, W. et al. 2011.[80] |
| Monocyte Macrophages | Promote anti-inflammatory and immunosuppressive CD163+macrophages via CCL2/CCR2 signaling aHSC attract Cx3cr1+Arg1+ macrophages via Cx3cl1 in the peritumoral area |
Enhanced production of anti-inflammatory cytokines; reduced pro-inflammatory responses Promote CD8+ T-cell suppression |
Xi, S. et al. 2021. [85] Ji, J. et al. 2015. [53] Otto, J. et al. 2023. [51] Jeong, J. M. et al. 2024. [197] |
| MDSCs | Promote MDSC conversion via CD44 and COX-2 secretion Depend on IFNγ signaling in HSCs Increase HCC migration and tumor sphere formation |
Increased immunosuppression and inflammation Promote HCC tumorigenesis |
Hochst, B. et al. 2013. [198] Xu, Y. et al. 2016. [199] Chou, H. S. et al. 2011. [71] Ji, J. et al. 2015. [53] Zhao, W. et al. 2012. [74] Dangi, A. et al. 2012.[75] Seki, E. et al. 2015. [200] |
| DCs | Inhibit DC maturation and cytokine production; upregulate DIgR2 expression | Impaired antigen presentation; reduced Th1 responses | Flavell, R. A. et al. 2010. [201] |
| NK-cells | Inhibit NK cell activity via TGF-β, PGE2, and ECM-associated mechanisms | Immune escape via reduction for tumor cell killing | Li, T. et al. 2012. [81] Shi, J. et al. 2017. [82] Katz, J. B. et al. 2008.[83] Becker, J. C. et al. 2013. [84] |
| Neutrophils | Induce PD-L1 expression on neutrophils through CAF-secreted mediators | Suppression of immune responses | Cheng, Y. et al. 2018. [202] |
Tregs, regulatory T-cells; MDSCs, myeloid-derived suppressor cells; DCs, Dendritic cells; ECM, Extracellular matrix.