期刊
CANCER IMMUNOLOGY RESEARCH
卷 10, 期 4, 页码 403-419出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-21-0588
关键词
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资金
- U.S. NIH [R01CA197363, U01CA217864]
- Cancer Research Institute as a Cancer Research Institute/Amgen Fellow
- Abbvie
- Amgen
- Bristol Myers Squibb
- Pfizer
In this study, the authors used single-cell RNA sequencing analysis to explore the diversity of myeloid cells in tumors and found that the transition from monocytes to macrophages is closely associated with the abundance of regulatory T cells and the quality of infiltrating T cells.
The tumor immune microenvironment (TIME) is commonly infiltrated by diverse collections of myeloid cells. Yet, the complexity of myeloid-cell identity and plasticity has challenged efforts to define bona fide populations and determine their connections to T-cell function and their relationship to patient outcome. Here, we have leveraged single-cell RNA-sequencing analysis of several mouse and human tumors and found that monocyte-macrophage diversity is characterized by a combination of conserved lineage states as well as transcriptional pro grams accessed along the differentiation trajectory. We also found in mouse models that tumor monocyte-to-macrophage progression was profoundly tied to regulatory T cell (Treg) abundance. In human kidney cancer, heterogeneity in macro-phage accumulation and myeloid composition corresponded to variance in, not only Treg density, but also the quality of infil-trating CD8 thorn T cells. In this way, holistic analysis of monocyte-to-macrophage differentiation creates a framework for critically different immune states.
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