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Interleukin 10-expressing B cells inhibit tumor-infiltrating T cell function and correlate with T cell Tim-3 expression in renal cell carcinoma

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Tumor Biology

Abstract

Renal cell carcinoma is among the leading causes of cancer-related death and was found to induce IL-10. We started by focusing on IL-10-secreting cells in tumor-infiltrating lymphocytes in renal cell carcinoma patients and observed that both CD3+ T cells and CD19+ B cells contributed to an elevated IL-10 expression. We then focused on IL-10-expressing B cells, and found that compared to non-IL-10-producing B cells, the IL-10-expressing B cells had significantly lower levels of CD19 and CD20 expression, a lack of IgM and IgD expression, while the level of CD27 was elevated. Moreover, culturing under unstimulated conditions resulted in higher antibody production by these IL-10-producing B cells than their peripheral blood counterparts, which strongly suggested that they are plasmablast-differentiating cells. Both IgA and IgG subtypes were found but IgA had a higher relative abundance in the tumor-infiltrating fraction. We then observed inverse correlations between the frequency of IL-10-producing B cells and pro-inflammatory cytokine-producing T cells and T cell proliferation. The expression of T cell exhaustion marker Tim-3, however, was upregulated in patients with high frequencies of IL-10-producing B cells. Moreover, supernatant from tumor B cells suppressed T cell inflammation. In addition, frequencies of IL-10-producing tumor-infiltrating B cells were inversely correlated with resected tumor size, and were higher in later stage tumors. Together, our data demonstrated that IL-10-producing B cells had plasmablast-differentiating phenotype, and could contribute to T cell immunosuppression in renal cell carcinoma.

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Acknowledgments

This work is supported by the National Natural Science Foundation of China (No.: 81202019).

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    Authors and Affiliations

    1. Department of Special Clinic, Changzheng Hospital, Second Military Medical University, Shanghai, 200433, China

      Chen Cai & Minyu Li

    2. Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China

      Jin Zhang

    3. Department of Urology, Changzheng Hospital, Second Military Medical University, Shanghai, 200433, China

      Zhen-Jie Wu & Lin-Hui Wang

    4. BGC Therapeutics and Research Laboratory, Vancouver, Canada

      Ken H. Song & Tina W. Zhan

    5. Department of Urology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, China

      Ying-Hao Sun

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    1. Chen Cai
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    2. Jin Zhang
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    3. Minyu Li
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    Correspondence to Lin-Hui Wang.

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    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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    Chen Cai and Jin Zhang contributed equally to this work.

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    Cai, C., Zhang, J., Li, M. et al. Interleukin 10-expressing B cells inhibit tumor-infiltrating T cell function and correlate with T cell Tim-3 expression in renal cell carcinoma. Tumor Biol. 37, 8209–8218 (2016). https://doi.org/10.1007/s13277-015-4687-1

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