Figure 2.

Suggestive model of tumor surveillance by liver T_RM cells. The liver CD8+ T_RM cells have been studied in several previous reports. They express CD69, but CD103 is expressed in the small portion among the CD69+ population in human. They express chemokine receptor type 6 (CXCR6) and lymphocyte function-associated antigen-1 (LFA-1) and persist in the liver tissue or liver sinusoid. Although their regulating factor is still unknown, liver CD8+ T_RM cells are considered to be functionally impaired or tolerant compared with the other T cell population. This might be associated with the priming by PD-L1-expressing hepatocytes. The CD103+ subpopulation is known to perform an anti-viral function, because they can highly secrete IL-2 and other effector molecules against hepatitis B virus (HBV) peptide stimulation. However, the characteristics of CD4+ T_RM cells and their role in the tumor surveillance are still unknown. T_RM-tumor equilibrium (left-right arrow) has not been studied in the HCC model, but as in other cancers, liver CD8+ T_RM cells might have a role in the surveillance against minimally residual tumor cells after HCC treatment, newly developed tumor cells, or circulating tumor cells that enter the liver tissue or sinusoid. This function of liver CD8+ T_RM cells could be enhanced by anti-PD-L1 or IL-2 treatment according to the previous report of murine skin cancer model or modulation of regulating factors of liver CD8+ T_RM cells, which needs to be elucidated in future studies. Each leftwards or rightwards arrow indicate that the one before the arrow affects the one after it. Question mark represents the hypothesis which is unclear.