Holistic Characterization of Tumor Monocyte-to-Macrophage Differentiation Integrates Distinct Immune Phenotypes in Kidney Cancer
| Autor: | Adriana M. Mujal, Alexis J. Combes, Arjun A. Rao, Mikhail Binnewies, Bushra Samad, Jessica Tsui, Alexandre Boissonnas, Joshua L. Pollack, Rafael J. Argüello, Maxwell V. Meng, Sima P. Porten, Megan K. Ruhland, Kevin C. Barry, Vincent Chan, Matthew F. Krummel |
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| Přispěvatelé: | University of California [San Francisco] (UC San Francisco), University of California (UC), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Massachusetts Institute of Technology (MIT) |
| Rok vydání: | 2022 |
| Předmět: |
Cancer Research
Kidney Disease [SDV]Life Sciences [q-bio] Macrophages Human Genome Oncology and Carcinogenesis Immunology Pharmacology and Pharmaceutical Sciences Article Monocytes Kidney Neoplasms Mice Phenotype Tumor Microenvironment Genetics Animals 2.1 Biological and endogenous factors Aetiology Cancer |
| Zdroj: | Cancer immunology research, vol 10, iss 4 Cancer Immunol Res Cancer Immunology Research Cancer Immunology Research, 2022, 10 (4), pp.403-419. ⟨10.1158/2326-6066.CIR-21-0588⟩ |
| ISSN: | 2326-6074 2326-6066 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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