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 Supplementary Figure S1 shows association of PD-1+ and PD-1high B cells in tumor tissue with disease recurrence, plasma HBV DNA and cytokines in HCC patients, and surface markers on HCC B cells. Supplementary Figure S2 shows gating strategies for FACS, and the phenotypic and functional features of the B cell subsets. Supplementary Figure S3 expands data on factors that modulate PD-1 expression on B cells in HCC. Supplementary Figure S4 expands data on roles of Bcl-6 and STAT6 in B cell PD-1 regulation. Supplementary Figure S5 expands data on effects of PD-1 agonist on B cells. Supplementary Figure S6 expands data on effects of PD-1 triggering by PD-L1-expressing cells. Supplementary Figure S7 expands data on triggering PD-1 in B cells suppresses tumor-specific immunity. Supplementary Figure S8 shows graphical abstract for the results. Supplementary Figure S9 shows Isotype staining of FACS and immunohistochemistry (IHC) using clinical samples. Supplementary Figure S10 shows the negative expression of monocyte subset markers in tumor B cells.
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
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
