| First Author | Lu Y | Year | 2020 |
| Journal | Cell | Volume | 180 |
| Issue | 6 | Pages | 1081-1097.e24 |
| PubMed ID | 32142650 | Mgi Jnum | J:348009 |
| Mgi Id | MGI:7627201 | Doi | 10.1016/j.cell.2020.02.015 |
| Citation | Lu Y, et al. (2020) Complement Signals Determine Opposite Effects of B Cells in Chemotherapy-Induced Immunity. Cell 180(6):1081-1097.e24 |
| abstractText | Understanding molecular mechanisms that dictate B cell diversity is important for targeting B cells as anti-cancer treatment. Through the single-cell dissection of B cell heterogeneity in longitudinal samples of patients with breast cancer before and after neoadjuvant chemotherapy, we revealed that an ICOSL(+) B cell subset emerges after chemotherapy. Using three immunocompetent mouse models, we recapitulated the subset switch of human tumor-infiltrating B cells during chemotherapy. By employing B-cell-specific deletion mice, we showed that ICOSL in B cells boosts anti-tumor immunity by enhancing the effector to regulatory T cell ratio. The signature of ICOSL(+) B cells is imprinted by complement-CR2 signaling, which is triggered by immunogenic cell death. Moreover, we identified that CD55, a complement inhibitory protein, determines the opposite roles of B cells in chemotherapy. Collectively, we demonstrated a critical role of the B cell subset switch in chemotherapy response, which has implications in designing novel anti-cancer therapies. VIDEO ABSTRACT. |
