PD-1 expression is elevated in monocytes from hepatocellular carcinoma patients and contributes to CD8 T cell suppression

It is recently shown that PD-1 expression by immune cells of the myeloid lineage contributes to the suppression of antitumor immunity. The expression of PD-1 by antigen-presenting cells in hepatocellular carcinoma (HCC), a malignancy with high intratumoral PD-L1 expression, remained understudied. Here, we found that circulating monocytes from HBV-associated HCC patients upregulated PD-1 in a severity-dependent manner. Monocyte stimulation using IFN-gamma or high levels of IL-10 could slightly increase PD-1 expression, while LPS could markedly increase PD-1 expression. Interestingly, LPS in combination with IL-4 or IL-10 presented stronger stimulation of PD-1 expression than LPS in combination with IFN-gamma or LPS alone. At resting state, PD-1(+)monocytes presented comparable MHC-I and IL-12 expression and higher MHC-II, CD86, iNOS, arginase I, and IL-10 expression than PD-1(-)monocytes. Upon LPS stimulation, PD-1(+)monocytes presented lower iNOS and higher arginase I and IL-10 expression than PD-1(-)monocytes, indicating an M2-polarization bias in PD-1(+)monocytes. CD8 T cells following coculture with PD-1(+)monocytes presented lower IFN-gamma and lower TNF-alpha expression, together with lower proliferation capacity, than CD8 T cells following coculture with PD-1(-)monocytes, suggesting that PD-1(+)monocytes were less capable of supporting CD8 T cell activation. Overall, these data indicated that PD-1 expression was elevated in monocytes from hepatocellular carcinoma patients. In addition, PD-1(+)monocytes presented a preference toward M2 polarization and had a deficiency in supporting CD8 T cells.