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

被引：1011

作者：

Zhang, Lei ^{[1
]}

Li, Ziyi ^{[2
,3
]}

Skrzypczynska, Katarzyna M. ^{[4
,5
]}

Fang, Qiao ^{[1
]}

Zhang, Wei ^{[6
]}

O'Brien, Sarah A. ^{[4
,5
]}

He, Yao ^{[1
]}

Wang, Lynn ^{[4
,5
]}

Zhang, Qiming ^{[2
,3
]}

Kim, Aeryon ^{[4
,5
]}

Gao, Ranran ^{[2
,3
]}

Orf, Jessica ^{[4
,5
]}

Wang, Tao ^{[2
,3
]}

Sawant, Deepali ^{[4
,5
]}

Kang, Jiajinlong ^{[2
,3
]}

Bhatt, Dev ^{[4
,5
]}

Lu, Daniel ^{[4
,5
]}

Li, Chi-Ming ^{[4
,5
]}

Rapaport, Aaron S. ^{[4
,5
]}

Perez, Kristy ^{[4
,5
]}

Ye, Yingjiang ^{[6
]}

Wang, Shan ^{[6
]}

Hu, Xueda ^{[2
,3
,7
]}

Ren, Xianwen ^{[2
,3
]}

Ouyang, Wenjun ^{[4
,5
]}

Shen, Zhanlong ^{[6
]}

Egen, Jackson G. ^{[4
,5
]}

Zhang, Zemin ^{[1
,2
,3
]}

Yu, Xin ^{[4
,5
]}

机构：

[1] Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing Adv Innovat Ctr Genom, Beijing 100871, Peoples R China

[2] Peking Univ, BIOPIC, Beijing 100871, Peoples R China

[3] Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China

[4] Amgen Inc, Amgen Res, Dept Inflammat & Oncol, San Francisco, CA 94080 USA

[5] Amgen Inc, Amgen Res, Genome Anal Unit, San Francisco, CA 94080 USA

[6] Peking Univ, Dept Gastroenterol Surg, Peoples Hosp, Beijing 100044, Peoples R China

[7] Analyt Biosci Ltd, Beijing 100084, Peoples R China

来源：

CELL | 2020年 / 181卷 / 02期

基金：

中国国家自然科学基金;

关键词：

TUMOR-ASSOCIATED MACROPHAGES; DENDRITIC CELLS; HETEROGENEITY; TISSUE; LANDSCAPE; ANTIBODY; INNATE; TRANSCRIPTOMES; ADENOCARCINOMA; IMMUNOTHERAPY;

D O I：

10.1016/j.cell.2020.03.048

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：442 / +

页数：46

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