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

Zhang, Lei, Li, Ziyi, Skrzypczynska, Katarzyna M., Fang, Qiao, Zhang, Wei, O’Brien, Sarah A., He, Yao, Wang, Lynn, Zhang, Qiming, Kim, Aeryon, Gao, Ranran, Orf, Jessica, Wang, Tao, Sawant, Deepali, Kang, Jiajinlong, Bhatt, Dev, Lu, Daniel, Li, Chi-Ming, Rapaport, Aaron S., Perez, Kristy, Ye, Yingjiang, Wang, Shan, Hu, Xueda, Ren, Xianwen, Ouyang, Wenjun, Shen, Zhanlong, Egen, Jackson G., Zhang, Zemin, Yu, Xin·2020·Cell
DOI 10.1016/j.cell.2020.03.048
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Abstract

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.

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Cited by

Metadata

Authors
Zhang, L., Li, Z., Skrzypczynska, K. M., Fang, Q., Zhang, W., O’Brien, S. A., He, Y., Wang, L., Zhang, Q., Kim, A., Gao, R., Orf, J., Wang, T., Sawant, D., Kang, J., Bhatt, D., Lu, D., Li, C.-M., Rapaport, A. S., Perez, K., Ye, Y., Wang, S., Hu, X., Ren, X., Ouyang, W., Shen, Z., Egen, J. G., Zhang, Z., & Yu, X.
Venue
Cell
Publisher
Elsevier BV
Published
2020-04
Volume
181
Issue
2
Pages
442-459.e29
ISSN
0092-8674
DOI
10.1016/j.cell.2020.03.048
Cited by
1,526
References
29
Language
en
Licence
Funders
  • National Natural Science Foundation of China
  • Amgen
  • Key Technologies Research and Development Program

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