Diverse Macrophage Populations Contribute to the Inflammatory Microenvironment in Premalignant Lesions During Localized Invasion

Ayman M. Ibrahim, Matthew A. Moss, Zane Gray, Michelle D. Rojo, Caitlin M. Burke, Kathryn L. Schwertfeger, Camila O. dos Santos, Heather L. Machado

Research output: Contribution to journalArticlepeer-review

Abstract

Myeloid cell heterogeneity remains poorly studied in breast cancer, and particularly in premalignancy. Here, we used single cell RNA sequencing to characterize macrophage diversity in mouse pre-invasive lesions as compared to lesions undergoing localized invasion. Several subpopulations of macrophages with transcriptionally distinct profiles were identified, two of which resembled macrophages in the steady state. While all subpopulations expressed tumor-promoting genes, many of the populations expressed pro-inflammatory genes, differing from reports in tumor-associated macrophages. Gene profiles of the myeloid cells were similar between early and late stages of premalignancy, although expansion of some subpopulations occurred. These results unravel macrophage heterogeneity in early progression and may provide insight into early intervention strategies that target macrophages.

Original languageEnglish (US)
Article number569985
JournalFrontiers in Oncology
Volume10
DOIs
StatePublished - Sep 24 2020

Bibliographical note

Funding Information:
The authors would like to thank Dr. Daniel Medina at Baylor College of Medicine for the PN1a transplantable model, Dr. Kejing Song at the Tulane Center for Translational Research in Infection & Immunity NextGen Sequencing Core, and Dr. James Jackson at Tulane School of Medicine for critical scientific discussion. Funding. This work was supported by an F31 fellowship (CA239445-01) to MR; NIH R01CA215052 and R01HD095858 to KS; CSHL and Northwell health affiliation, The Rita Allen Scholar Award, AACR-Breast Cancer Research Foundation Award, The Pershing Square Sohn Prize for Cancer Research, and NIH R01CA248158-01 to Cods; Carol Lavin Bernick Grant and NIH R01CA212518 to HM.

Keywords

  • localized invasion
  • macrophage
  • microenvironment
  • mouse model
  • premalignancy
  • scRNA sequencing

PubMed: MeSH publication types

  • Journal Article

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