Faculty, Staff and Student Publications
Publication Date
2-7-2022
Journal
Journal of Experimental Medicine
Abstract
Tumor-associated macrophages (TAMs) are correlated with the progression of prostatic adenocarcinoma (PCa). The mechanistic basis of this correlation and therapeutic strategies to target TAMs in PCa remain poorly defined. Here, single-cell RNA sequencing was used to profile the transcriptional landscape of TAMs in human PCa, leading to identification of a subset of macrophages characterized by dysregulation in transcriptional pathways associated with lipid metabolism. This subset of TAMs correlates positively with PCa progression and shorter disease-free survival and is characterized by an accumulation of lipids that is dependent on Marco. Mechanistically, cancer cell-derived IL-1β enhances Marco expression on macrophages, and reciprocally, cancer cell migration is promoted by CCL6 released by lipid-loaded TAMs. Moreover, administration of a high-fat diet to tumor-bearing mice raises the abundance of lipid-loaded TAMs. Finally, targeting lipid accumulation by Marco blockade hinders tumor growth and invasiveness and improves the efficacy of chemotherapy in models of PCa, pointing to combinatorial strategies that may influence patient outcomes.
Keywords
Animals, Cell Plasticity, Cytokines, Disease Models, Animal, Disease Progression, Gene Expression Profiling, Gene Knockdown Techniques, Heterografts, Humans, Lipid Metabolism, Lipids, Male, Metabolic Networks and Pathways, Mice, Prostatic Neoplasms, Single-Cell Analysis, Tumor Microenvironment, Tumor-Associated Macrophages
DOI
10.1084/jem.20210564
PMID
34919143
PMCID
PMC8932635
PubMedCentral® Posted Date
12-17-2021
PubMedCentral® Full Text Version
Post-print
Graphical Abstract
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons