研究揭示B細胞和濾泡輔助T細胞在乳腺癌中的新功能
作者：
小柯機器人發布時間：2019/11/15 12:48:49
美國北卡羅來納大學Charles M. Perou研究組提出，在高突變負荷的乳腺癌小鼠模型中，B細胞和濾泡輔助T細胞介導對檢查點抑制劑的應答。該項研究成果發表在2019年11月14日出版的《細胞》上。
通過建立新的乳腺腫瘤模型，研究人員發現腫瘤突變負荷和特定免疫細胞的反應相關。此外，研究人員從敏感和耐藥的小鼠模型中，獲得了經過免疫治療和未治療的腫瘤豐富的單細胞RNA-seq和大量mRNA-seq數據。使用這種方法，研究人員發現免疫檢查點療法可誘導B細胞的濾泡輔助性T細胞活化，從而促進這些模型中小鼠的抗腫瘤反應。研究人員還發現，T細胞的B細胞活化和抗體的產生是免疫療法反應的關鍵，並為免疫檢查點療法提供了新的生物標記物。總的來說，這項工作建立了乳腺癌臨床前新模型，並提供了針對治療敏感個體的mRNA-seq和單細胞RNA-seq資料庫，還揭示了應對免疫檢查點抑制劑反應的新成分。
據悉，這項研究使用三陰性乳腺癌小鼠模型確定了介導免疫檢查點抑制劑反應的機制。
附：英文原文
Title: B Cells and T Follicular Helper Cells Mediate Response to Checkpoint Inhibitors in High Mutation Burden Mouse Models of Breast Cancer
Author: Daniel P. Hollern, Nuo Xu, Aatish Thennavan, Cherise Glodowski, Susana Garcia-Recio, Kevin R. Mott, Xiaping He, Joseph P. Garay, Kelly Carey-Ewend, David Marron, John Ford, Siyao Liu, Sarah C. Vick, Miguel Martin, Joel S. Parker, Benjamin G. Vincent, Jonathan S. Serody, Charles M. Perou
Issue&Volume: 2019/11/14
Abstract: This study identifies mechanisms mediating responses to immune checkpoint inhibitors using mouse models of triple-negative breast cancer. By creating new mammary tumor models, we find that tumor mutation burden and specific immune cells are associated with response. Further, we developed a rich resource of single-cell RNA-seq and bulk mRNA-seq data of immunotherapy-treated and non-treated tumors from sensitive and resistant murine models. Using this, we uncover that immune checkpoint therapy induces T follicular helper cell activation of B cells to facilitate the anti-tumor response in these models. We also show that B cell activation of T cells and the generation of antibody are key to immunotherapy response and propose a new biomarker for immune checkpoint therapy. In total, this work presents resources of new preclinical models of breast cancer with large mRNA-seq and single-cell RNA-seq datasets annotated for sensitivity to therapy and uncovers new components of response to immune checkpoint inhibitors.
DOI: 10.1016/j.cell.2019.10.028
Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31178-X
Cell：《細胞》，創刊於1974年。隸屬於細胞出版社，最新IF：36.216