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Single-cell RNA-seq of B cell polustion in breast cancer patients

ABSTRACT: Re-education of immune cells in tumor microenvironment is required for optimal treatment outcome. The prevailing notion is that B cells, a major immune cell type in tumors, are immunosuppressive and pro-tumoral. However, why B cells inhibit tumor progression in certain contexts remains unexplained. By single cell dissection of B cell heterogeneity in longitudinal samples of breast cancer patients before and after neoadjuvant chemotherapy, we revealed a distinct subset of B cells emerges after chemotherapy, which is predictive for therapeutic efficacy and prognosis in multiple patient cohorts. Using three immunocompetent mouse models, our in vivo experiments faithfully recapitulated the subset switch of human tumor-infiltrating B cells during chemotherapy. Employing B-specific deletion and adoptive transfer experiment, we showed that ICOSL in this B cell subset boosts anti-tumor immunity by enhancing the ratio of effector and regulatory T cells. The signature of ICOSL+ B cell subset is imprinted by complement-CR2 signaling, which is triggered by chemotherapy-induced immunogenic tumor cell death. Moreover, by screening the cell line encyclopedia, we identified CD55, a complement inhibitory protein, determines the dual roles of B cells in the response of various malignancies to chemotherapy. Collectively, our study demonstrates a critical role of B cell subset switch in chemotherapy response and have implications for designing novel therapeutic approaches.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE135710 | GEO | 2020/03/13

REPOSITORIES: GEO

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