title: Interleukin 10-expressing B cells inhibit tumor-infiltrating T cell function and correlate with T cell Tim-3 expression in renal cell carcinoma.
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.
authors.affiliation: Department of Special Clinic, Changzheng Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Cai
authors.affiliation: Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Special Clinic, Changzheng Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Minyu
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Urology, Changzheng Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Zhen-Jie
authors.initials: ZJ
authors.lastname: Wu
authors.affiliation: BGC Therapeutics and Research Laboratory, Vancouver, Canada.
authors.forename: Ken H
authors.initials: KH
authors.lastname: Song
authors.affiliation: BGC Therapeutics and Research Laboratory, Vancouver, Canada.
authors.forename: Tina W
authors.initials: TW
authors.lastname: Zhan
authors.affiliation: Department of Urology, Changzheng Hospital, Second Military Medical University, Shanghai, 200433, China. linhuiwang_sh@126.com.
authors.forename: Lin-Hui
authors.initials: LH
authors.lastname: Wang
authors.affiliation: Department of Urology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, China.
authors.forename: Ying-Hao
authors.initials: YH
authors.lastname: Sun
mesh_terms: D000368:Aged; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D000072597:Hepatitis A Virus Cellular Receptor 2 / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000556:secondary; D008207:Lymphatic Metastasis; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D016207:Cytokines; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; C508609:IL10 protein, human; D018836:Inflammation Mediators; D016753:Interleukin-10
keywords: IL-10; Renal cell carcinoma; Tumor-infiltrating lymphocytes