@article{31a166c5a9134da0b2756c56d22e042b,
title = "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 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.",
author = "Mujal, {Adriana M.} and Combes, {Alexis J.} and Rao, {Arjun A.} and Mikhail Binnewies and Bushra Samad and Jessica Tsui and Alexandre Boissonnas and Pollack, {Joshua L.} and Arg€uello, {Rafael J.} and Meng, {Maxwell V.} and Porten, {Sima P.} and Ruhland, {Megan K.} and Barry, {Kevin C.} and Vincent Chan and Krummel, {Matthew F.}",
note = "Funding Information: This work was supported by the U.S. NIH (R01CA197363 and U01CA217864, to M.F. Krummel). A.M. Mujal is supported by the Cancer Research Institute as a Cancer Research Institute/Amgen Fellow. Acquisition and analysis of certain human samples was partially funded by contributions from Abbvie, Amgen, Bristol Myers Squibb, and Pfizer as part of the UCSF Immunoprofiler Initiative. Funding Information: submitted work. M.F. Krummel reports grants from NIH, Abbvie, Amgen, Bristol Myers Squibb, and Pfizer during the conduct of the study; other support from Pionyr Immunotherapeutics and Founder Innovations|Studios outside the submitted work. No disclosures were reported by the other authors. Publisher Copyright: {\textcopyright} 2022 American Association for Cancer Research.",
year = "2022",
month = apr,
doi = "10.1158/2326-6066.CIR-21-0588",
language = "English (US)",
volume = "10",
pages = "403--419",
journal = "Cancer immunology research",
issn = "2326-6066",
publisher = "American Association for Cancer Research Inc.",
number = "4",
}