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

Author information

Affiliations

  • 1. Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China. State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
      Authors
    • Xiao X 1
    • Zheng L 1
    (2 authors)
  • 2. State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
      Authors
    • Lao XM 2
    • Kuang DM 2
    (2 authors)
  • 3. Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
      Authors
    • Chen MM 3
    • Liu RX 3
    • Wei Y 3
    • Ouyang FZ 3
    • Chen DP 3
    • Zhao XY 3
    • Li XF 3
    • Liu CL 3
    (8 authors)
  • 4. Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China. Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
      Authors
    • Zhao Q 4
    (1 author)

ORCIDs linked to this article

Show all (8)

Cancer Discovery, 29 Feb 2016, 6(5):546-559
https://doi.org/10.1158/2159-8290.cd-15-1408 PMID: 26928313 

A comment on this article appears in "PD-1 Shapes B Cells as Evildoers in the Tumor Microenvironment." Cancer Discov. 2016 May;6(5):477-8.

Abstract 

Unlabelled

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-1(hi) B cells exhibited a unique CD5(hi)CD24(-/+)CD27(hi/+)CD38(dim) phenotype different from the phenotype of conventional CD24(hi)CD38(hi) peripheral regulatory B cells. TLR4-mediated BCL6 upregulation was crucial for PD-1(hi) 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-1(hi) 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-1(hi) 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-1(hi) 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. 477This article is highlighted in the In This Issue feature, p. 461.

Full text links 

Read article at publisher's site: https://doi.org/10.1158/2159-8290.cd-15-1408

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    Funding 

    Funders who supported this work.

    Doctoral Dissertation of PR China (1)

    Fundamental Research Funds for the Central Universities (1)

    Guangdong Natural Science Funds for Distinguished Young Scholars (1)

    National Natural Science Foundation of China (3)