Holistic Characterization of Tumor Monocyte-to-Macrophage Differentiation Integrates Distinct Immune Phenotypes in Kidney Cancer

Adriana M. Mujal, Alexis J. Combes, Arjun A. Rao, Mikhail Binnewies, Bushra Samad, Jessica Tsui, Alexandre Boissonnas, Joshua L. Pollack, Rafael J. Arg€uello, Maxwell V. Meng, Sima P. Porten, Megan K. Ruhland, Kevin C. Barry, Vincent Chan, Matthew F. Krummel

Research output: Contribution to journalArticlepeer-review

Abstract

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 programs 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 macrophage accumulation and myeloid composition corresponded to variance in, not only Treg density, but also the quality of infiltrating CD8 T cells. In this way, holistic analysis of monocyteto- macrophage differentiation creates a framework for critically different immune states.

Original languageEnglish (US)
Pages (from-to)403-419
Number of pages17
JournalCancer Immunology Research
Volume10
Issue number4
DOIs
StatePublished - Apr 2022
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

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