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Article Dans Une Revue Cancer Immunology Research Année : 2022

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

Adriana Mujal
  • Fonction : Auteur
Alexis Combes
  • Fonction : Auteur
Arjun Rao
  • Fonction : Auteur
Mikhail Binnewies
  • Fonction : Auteur
Bushra Samad
Jessica Tsui
  • Fonction : Auteur
Joshua Pollack
  • Fonction : Auteur
Rafael Argüello
Maxwell Meng
  • Fonction : Auteur
Sima Porten
  • Fonction : Auteur
Megan Ruhland
Kevin Barry
Vincent Chan
  • Fonction : Auteur
Matthew Krummel
  • Fonction : Auteur

Résumé

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 monocyte-to-macrophage differentiation creates a framework for critically different immune states.

Dates et versions

hal-03451508 , version 1 (26-11-2021)
hal-03451508 , version 3 (26-11-2021)
hal-03451508 , version 2 (10-02-2023)

Identifiants

Citer

Adriana Mujal, Alexis Combes, Arjun Rao, Mikhail Binnewies, Bushra Samad, et al.. Holistic Characterization of Tumor Monocyte-to-Macrophage Differentiation Integrates Distinct Immune Phenotypes in Kidney Cancer. Cancer Immunology Research, 2022, 10 (4), pp.403-419. ⟨10.1158/2326-6066.CIR-21-0588⟩. ⟨hal-03451508v2⟩
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