Fig. 3.

Cancer immunosurveillance (cancer immunoediting) is impaired in NAFLD/NASH-HCC. In NASH-HCC, CD8⁺PD-1⁺ T cells are not activated in a classical manner, i.e., activation via antigen presentation by MHC class I. Therefore, in the immune elimination phase, the CD8⁺PD-1⁺ T cell (CXCR6⁺CD8⁺ T cell) cannot eliminate the cancer cell since this CD8⁺ T cell cannot recognize the cancer antigen. Similarly, in the escape phase, since immune escape is not related to the PD-1/PD-L1 binding mechanism, the anti-PD-1 antibody is theoretically not effective for restoring anti-cancer T cell activity. TAA, tumor-associated antigen; MHC, major histocompatibility complex; MDSC, myeloid-derived suppressor cell; Treg, regulatory T cells; MSC, mesenchymal stem cell; TAM, tumor-associated macrophage; CAF, cancer-associated fibroblast.