Single-Cell Analyses Inform Mechanisms of Myeloid-Targeted Therapies in Colon Cancer.

作者：Lei Zhang, Ziyi Li, Katarzyna M. Skrzypczynska, Qiao Fang, Wei Zhang, Sarah A. O’Brien, Yao He, Lynn Wang, Qiming Zhang, Aeryon Kim, Ranran Gao, Jessica Orf, Tao Wang, Deepali V. Sawant, Jiajinlong Kang, Dev Bhatt, Daniel R Lu, Chi-Ming Li, Aaron S. Rapaport, Kristy Perez, Yingjiang Ye, Shan Wang, Xueda Hu, Xianwen Ren, W. Ouyang, Zhanlong Shen, J. Egen, Zemin Zhang, Xin Yu · 发表于：Cell · 年份：2020 · DOI：10.1016/j.cell.2020.03.048 · 被引用次数：1314 · 研究领域：Medicine、Biology

Single-cell RNA sequencing (scRNA-seq) is a powerful tool for defining cellular diversity in tumors, but its application toward dissecting mechanisms underlying immune-modulating therapies is scarce. We performed scRNA-seq analyses on immune and stromal populations from colorectal cancer patients, identifying specific macrophage and conventional dendritic cell (cDC) subsets as key mediators of cellular cross-talk in the tumor microenvironment. Defining comparable myeloid populations in mouse tumors enabled characterization of their response to myeloid-targeted immunotherapy. Treatment with anti-CSF1R preferentially depleted macrophages with an inflammatory signature but spared macrophage populations that in mouse and human expresses pro-angiogenic/tumorigenic genes. Treatment with a CD40 agonist antibody preferentially activated a cDC population and increased Bhlhe40+ Th1-like cells and CD8+ memory T cells. Our comprehensive analysis of key myeloid subsets in human and mouse identifies critical cellular interactions regulating tumor immunity and defines mechanisms underlying myeloid-targeted immunotherapies currently undergoing clinical testing.