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Overrepresentation of IL-10-Expressing B Cells Suppresses Cytotoxic CD4+ T Cell Activity in HBV-Induced Hepatocellular Carcinoma.
- Source :
- PLoS ONE; 5/2/2016, Vol. 11 Issue 5, p1-11, 11p
- Publication Year :
- 2016
-
Abstract
- Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis and low five-year survival rate. A strong and effective CD4<superscript>+</superscript> T cell-mediated cytotoxicity was associated with better survival and low recurrence rate in HCC, but the regulatory mechanism that controls CD4<superscript>+</superscript> T cell cytotoxicity in HCC patients is not fully examined. Given that IL-10-expressing B cells could suppress the inflammation of cytotoxic CD8<superscript>+</superscript> 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<superscript>+</superscript> T cells. Surface molecule Tim-1 was preferentially expressed on IL-10-expressing B cells. Therefore, we separated total B cells into Tim-1<superscript>+</superscript> and Tim-1<superscript>-</superscript> B cells. CD4<superscript>+</superscript> T cells incubated with Tim-1<superscript>+</superscript> B cells exhibited significantly reduced levels of granzyme A, granzyme B and perforin expression, compared to the CD4<superscript>+</superscript> T cells incubated with Tim-1<superscript>-</superscript> B cells. Antagonizing IL-10 in culture rescued CD4<superscript>+</superscript> 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<superscript>+</superscript> cytotoxic T cells was downregulated. The negative correlations between IL-10-expressing B cells and CD4<superscript>+</superscript> 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- LIVER cancer
INTERLEUKIN-10
B cells
CYTOTOXIC T cells
SUPPRESSOR cells
PROGNOSIS
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 11
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- 115054490
- Full Text :
- https://doi.org/10.1371/journal.pone.0154815