Supplementary Methods from PD-1hi Identifies a Novel Regulatory B-cell Population in Human Hepatoma That Promotes Disease Progression

Xiao, Xiao; Lao, Xiang-Ming; Chen, Min-Min; Liu, Rui-Xian; Wei, Yuan; Ouyang, Fang-Zhu; Chen, Dong-Ping; Zhao, Xiao-Yu; Zhao, Qiyi; Li, Xue-Feng; Liu, Chuan-Lu; Zheng, Limin; Kuang, Dong-Ming

doi:10.1158/2159-8290.22530921.v1

Supplementary Methods from PD-1<sup>hi</sup> Identifies a Novel Regulatory B-cell Population in Human Hepatoma That Promotes Disease Progression

https://doi.org/10.1158/2159-8290.22530921

journal contribution

posted on 2023-04-03, 21:00 authored by Xiao Xiao, Xiang-Ming Lao, Min-Min Chen, Rui-Xian Liu, Yuan Wei, Fang-Zhu Ouyang, Dong-Ping Chen, Xiao-Yu Zhao, Qiyi Zhao, Xue-Feng Li, Chuan-Lu Liu, Limin Zheng, Dong-Ming Kuang

<p>Flow Cytometry, ELISA, Construction of Viral Vectors, and PD-L1/PD-L2 Stable Cell Lines.</p>

Funding

National Natural Science Foundation of China

Guangdong Natural Science Funds for Distinguished Young Scholars

Doctoral Dissertation of PR China

Fundamental Research Funds for the Central Universities

History

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1.
DOI - Is supplement to PD-1hi Identifies a Novel Regulatory B-cell Population in Human Hepatoma That Promotes Disease Progression

ARTICLE ABSTRACT

B cells often constitute abundant cellular components in human tumors. Regulatory B cells that are functionally defined by their ability to produce IL10 downregulate inflammation and control T-cell immunity. Here, we identified a protumorigenic subset of B cells that constitutively expressed higher levels of programmed cell death-1 (PD-1) and constituted ∼10% of all B cells in advanced-stage hepatocellular carcinoma (HCC). These PD-1hi B cells exhibited a unique CD5hiCD24−/+CD27hi/+CD38dim phenotype different from the phenotype of conventional CD24hiCD38hi peripheral regulatory B cells. TLR4-mediated BCL6 upregulation was crucial for PD-1hi B-cell induction by HCC environmental factors, and that effect was abolished by IL4-elicited STAT6 phosphorylation. Importantly, upon encountering PD-L1+ cells or undergoing PD-1 triggering, PD-1hi B cells acquired regulatory functions that suppressed tumor-specific T-cell immunity and promoted cancer growth via IL10 signals. Our findings provide significant new insights for human cancer immunosuppression and anticancer therapies regarding PD-1/PD-L1.Significance: We identify a novel protumorigenic PD-1hi B-cell subset in human HCC that exhibits a phenotype distinct from that of peripheral regulatory B cells. TLR4-mediated BCL6 upregulation is critical for induction of PD-1hi B cells, which operate via IL10-dependent pathways upon interacting with PD-L1 to cause T-cell dysfunction and foster disease progression. Cancer Discov; 6(5); 546–59. ©2016 AACR.See related commentary by Ren et al., p. 477.This article is highlighted in the In This Issue feature, p. 461