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Overrepresentation of IL-10-Expressing B Cells Suppresses Cytotoxic CD4+ T Cell Activity in HBV-Induced Hepatocellular Carcinoma
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Overrepresentation of IL-10-Expressing B Cells Suppresses Cytotoxic CD4+ T Cell Activity in HBV-Induced Hepatocellular Carcinoma
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Overrepresentation of IL-10-Expressing B Cells Suppresses Cytotoxic CD4+ T Cell Activity in HBV-Induced Hepatocellular Carcinoma
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Journal Article
Overrepresentation of IL-10-Expressing B Cells Suppresses Cytotoxic CD4+ T Cell Activity in HBV-Induced Hepatocellular Carcinoma
2016
Overview
Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis and low five-year survival rate. A strong and effective CD4+ T cell-mediated cytotoxicity was associated with better survival and low recurrence rate in HCC, but the regulatory mechanism that controls CD4+ T cell cytotoxicity in HCC patients is not fully examined. Given that IL-10-expressing B cells could suppress the inflammation of cytotoxic CD8+ T cells, T helper 1 (Th1) cells and Th17 cells, while promoting regulatory T (Treg) cell differentiation, we examined the role of IL-10-expressing B cells in HBV-related HCC patients. We found that compared to healthy controls, HCC patients exhibited significantly higher frequencies of IL-10-expressing B cells, which were negatively correlated with the frequencies of granzyme A, granzyme B, and perforin expressing CD4+ T cells. Surface molecule Tim-1 was preferentially expressed on IL-10-expressing B cells. Therefore, we separated total B cells into Tim-1+ and Tim-1- B cells. CD4+ T cells incubated with Tim-1+ B cells exhibited significantly reduced levels of granzyme A, granzyme B and perforin expression, compared to the CD4+ T cells incubated with Tim-1- B cells. Antagonizing IL-10 in culture rescued CD4+ T cell cytotoxicity. Compared to that in peripheral blood, the level of IL-10-expressing B cells were further upregulated in resected tumor, while the level of CD4+ cytotoxic T cells was downregulated. The negative correlations between IL-10-expressing B cells and CD4+ cytotoxic T cells were also observed in tumor-infiltrating cells. Together, our data revealed an additional antitumor mechanism mediated by IL-10-expressing B cells.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Carcinoma, Hepatocellular - metabolism
/ CD4-Positive T-Lymphocytes - metabolism
/ CD8-Positive T-Lymphocytes - metabolism
/ Female
/ Hepatitis A Virus Cellular Receptor 1 - metabolism
/ Hepatitis B virus - pathogenicity
/ Humans
/ Male
/ Medicine and Health Sciences
/ Patients
/ Perforin
/ Regulatory mechanisms (biology)
/ Surgery
/ Survival
/ T-Lymphocytes, Regulatory - metabolism
/ Toxicity
