PD-1 expression is elevated in monocytes from hepatocellular carcinoma patients and contributes to CD8 T cell suppressio
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ORIGINAL ARTICLE
PD-1 expression is elevated in monocytes from hepatocellular carcinoma patients and contributes to CD8 T cell suppression Jin Yun 1,2 & Genhua Yu 3 & Pingping Hu 2,4 & Yang Chao 1,2 & Xingyu Li 1,2 & Xiaobo Chen 1,2 & Qichun Wei 3 & Junfeng Wang 1,2,4 Received: 4 June 2020 / Accepted: 15 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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-γ 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-γ 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-γ and lower TNF-α 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. Keywords PD-1 . Monocyte . Hepatocellular carcinoma . CD8 T cell
Introduction
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12026-020-09155-3) contains supplementary material, which is available to authorized users. * Qichun Wei [email protected] * Junfeng Wang [email protected] 1
Department of Hepatobiliary Surgery, The First People’s Hospital of Yunnan Province, Kunming, Yunnan, China
2
The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China
3
Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
4
Department of Digital Medical Research Center, The First People’s Hospital of Yunnan Province, Kunming, Yunnan, China
Programmed death 1 (PD-1) and its ligand PD-L1 mediate a major inhibitory pathway in the immune system [1]. In T cells, PD-1 expression is upregulated upon activation. In the cases of chronic viral infections and malignancies, constant exposure to antigen
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