Title: B Cells and T Follicular Helper Cells Mediate Response to Checkpoint Inhibitors in High Mutation Burden Mouse Models of Breast Cancer.

Authors: Hollern, Daniel P; Xu, Nuo; Thennavan, Aatish; Glodowski, Cherise; Garcia-Recio, Susana; Mott, Kevin R; He, Xiaping; Garay, Joseph P; Carey-Ewend, Kelly; Marron, David; Ford, John; Liu, Siyao; Vick, Sarah C; Martin, Miguel; Parker, Joel S; Vincent, Benjamin G; Serody, Jonathan S; Perou, Charles M

Published In Cell, (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.

PubMed ID: 31730857

MeSH Terms: No MeSH terms associated with this publication