Tumor-associated macrophages in the cutaneous SCC microenvironment are heterogeneously activated

Julia S. Pettersen, Judilyn Fuentes-Duculan, Mayte Suárez-Farĩas, Katherine C. Pierson, Alexander Pitts-Kiefer, Linda Fan, Daniel A. Belkin, Claire Q F Wang, Shivaprasad Bhuvanendran, Leanne M. Johnson-Huang, Mark J. Bluth, James G. Krueger, Michelle A. Lowes, John A. Carucci

Research output: Contribution to journalArticle

97 Scopus citations

Abstract

Tumor-associated macrophages (TAMs) may have an important role in tumor immunity. We studied the activation state of TAMs in cutaneous SCC, the second most common human cancer. CD163+ was identified as a more abundant, sensitive, and accurate marker of TAMs when compared with CD68. CD163 TAMs produced protumoral factors, matrix metalloproteinases 9 and 11 (MMP9 and MMP11), at the gene and protein levels. Gene set enrichment analysis (GSEA) was used to evaluate M1 and M2 macrophage gene sets in the SCC genes and to identify candidate genes in order to phenotypically characterize TAMs. There was coexpression of CD163 and alternatively activated M2 markers, CD209 and CCL18 (chemokine (C-C motif) ligand 18). There was enrichment for classically activated M1 genes in SCC, which was confirmed in situ by colocalization of CD163 and phosphorylated STAT1 (signal transducer and activator of transcription 1), IL-23p19, IL-12/IL-23p40, and CD127. Also, a subset of TAMs in SCC was bi-activated as CD163 cells expressed markers for both M1 and M2, shown by triple-label immunofluorescence. These data support heterogeneous activation states of TAMs in SCC, and suggest that a dynamic model of macrophage activation would be more useful to characterize TAMs.

Original languageEnglish (US)
Pages (from-to)1322-1330
Number of pages9
JournalJournal of Investigative Dermatology
Volume131
Issue number6
DOIs
StatePublished - Jun 2011
Externally publishedYes

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

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    Pettersen, J. S., Fuentes-Duculan, J., Suárez-Farĩas, M., Pierson, K. C., Pitts-Kiefer, A., Fan, L., Belkin, D. A., Wang, C. Q. F., Bhuvanendran, S., Johnson-Huang, L. M., Bluth, M. J., Krueger, J. G., Lowes, M. A., & Carucci, J. A. (2011). Tumor-associated macrophages in the cutaneous SCC microenvironment are heterogeneously activated. Journal of Investigative Dermatology, 131(6), 1322-1330. https://doi.org/10.1038/jid.2011.9