biostudies-literatureHollern DPBreast Cancer Research FoundationCorsorcio Centro de Investigación Biomédica en RedNCISusan G. KomenNIEHS NIH HHSNCI NIH HHSCIHR1191-1206.e21https://www.ebi.ac.uk/biostudies/studies/S-EPMC6911685biostudies-literatureUnknown179(5)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 prCellB Cells and T Follicular Helper Cells Mediate Response to Checkpoint Inhibitors in High Mutation Burden Mouse Models of Breast Cancer.PMC6911685RO1-CA195740P50 CA058223R01 CA195740R01 CA148761P50-CA58223PDF17479425CA210427P30 ES010126SAC-160074T32 CA071341RO1-CA148761Ford JXu NGlodowski CMott KRVincent BGParker JSSerody JSPerou CMGarcia-Recio SLiu SMarron DGaray JPHollern DPThennavan ACarey-Ewend KHe XMartin MVick SCfalseB Cells and T Follicular Helper Cells Mediate Response to Checkpoint Inhibitors in High Mutation Burden Mouse Models of Breast Cancer.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 pr2019-01-01T00:00:00Z2019 Nov2026-05-04T19:42:47.147Z2020-11-19T16:59:03ZS-EPMC69116853173085710.1016/j.cell.2019.10.028