Holistic Characterization of Tumor Monocyte-to-Macrophage Differentiation Integrates Distinct Immune Phenotypes in Kidney Cancer
Holistic Characterization of Tumor Monocyte-to-Macrophage Differentiation Integrates Distinct Immune Phenotypes in Kidney Cancer
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 relation to patient outcome. Here we leverage single-cell RNA-sequencing (scRNA-seq) analysis of several mouse and human tumors and find that monocyte-macrophage diversity is characterized by a combination of conserved lineage states as well as transcriptional programs accessed along the differentiation trajectory. Using mouse models, we also find that tumor monocyte-to-macrophage progression is profoundly tied to regulatory T cell (Treg) abundance. Importantly, 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 in kidney tumors.
Mujal Adriana M.、Combes Alexis J.、Rao Arjun R.、Samad Bushra、Barry Kevin C.、Chan Vincent、Boissonnas Alexandre、Ruhland Megan K.、Arg¨1ello Rafael J.、Tsui Jessica、Binnewies Mikhail、Krummel Matthew F.、Pollack Joshua L.
Department of Pathology and ImmunoX||Immunology Program, Memorial Sloan Kettering Cancer CenterDepartment of Pathology and ImmunoX||UCSF CoLabs||UCSF Immunoprofiler InitiativeUCSF CoLabs||UCSF Immunoprofiler InitiativeDepartment of Pathology and ImmunoX||UCSF CoLabs||UCSF Immunoprofiler InitiativeDepartment of Pathology and ImmunoXDepartment of Pathology and ImmunoX||UCSF CoLabs||UCSF Immunoprofiler InitiativeSorbonne Universit¨|, INSERM, CNRS, Centre d?ˉImmunologie et des Maladies Infectieuses Cimi-ParisDepartment of Pathology and ImmunoXAix Marseille Univ, CNRS, INSERM, CIML, Centre d?ˉImmunologie de Marseille-LuminyDepartment of Pathology and ImmunoX||UCSF CoLabs||UCSF Immunoprofiler InitiativeDepartment of Pathology and ImmunoXDepartment of Pathology and ImmunoX||UCSF CoLabs||UCSF Immunoprofiler InitiativeUCSF Immunoprofiler Initiative
肿瘤学基础医学分子生物学
Mujal Adriana M.,Combes Alexis J.,Rao Arjun R.,Samad Bushra,Barry Kevin C.,Chan Vincent,Boissonnas Alexandre,Ruhland Megan K.,Arg¨1ello Rafael J.,Tsui Jessica,Binnewies Mikhail,Krummel Matthew F.,Pollack Joshua L..Holistic Characterization of Tumor Monocyte-to-Macrophage Differentiation Integrates Distinct Immune Phenotypes in Kidney Cancer[EB/OL].(2025-03-28)[2025-04-27].https://www.biorxiv.org/content/10.1101/2021.07.07.451502.点此复制
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