Single-Cell Analyses Inform Mechanisms of Myeloid-Targeted Therapies in Colon Cancer
| Autor: | Shan Wang, Aaron S. Rapaport, Yao He, Daniel Lu, Xin Yu, Lynn Wang, Yingjiang Ye, Jackson G. Egen, Xueda Hu, Qiao Fang, Ranran Gao, Lei Zhang, Xianwen Ren, Jessica Orf, Aeryon Kim, Wenjun Ouyang, Qiming Zhang, Deepali V. Sawant, Wei Zhang, Chi-Ming Li, Katarzyna M. Skrzypczynska, Kristy Perez, Zhanlong Shen, Jiajinlong Kang, Ziyi Li, Dev Bhatt, Sarah A. O’Brien, Zemin Zhang, Tao Wang |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male China Stromal cell Myeloid medicine.medical_treatment Population Biology CD8-Positive T-Lymphocytes General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Mice 0302 clinical medicine Immune system medicine Tumor Microenvironment Animals Humans Myeloid Cells education 030304 developmental biology Aged Aged 80 and over 0303 health sciences education.field_of_study Tumor microenvironment CD40 Base Sequence Sequence Analysis RNA Macrophages Immunotherapy Dendritic Cells Middle Aged medicine.anatomical_structure Colonic Neoplasms Cancer research biology.protein Female Single-Cell Analysis Colorectal Neoplasms 030217 neurology & neurosurgery Conventional Dendritic Cell |
| Zdroj: | Cell. 181(2) |
| ISSN: | 1097-4172 |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
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