Tumor-Associated Macrophages in the Cutaneous SCC Microenvironment Are Heterogeneously Activated

Julia S. Pettersen, Judilyn Fuentes-Duculan, Mayte Suárez-Fariñas, 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

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.Journal of Investigative Dermatology advance online publication, 10 February 2011; doi:10.103/jid.2011.9.

Original languageEnglish (US)
JournalJournal of Investigative Dermatology
DOIs
StateAccepted/In press - Feb 10 2011
Externally publishedYes

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Macrophages
Tumors
Skin
Neoplasms
Genes
Chemical activation
Interleukin-23 Subunit p19
Matrix Metalloproteinase 11
STAT1 Transcription Factor
Dermatology
CC Chemokines
Gene Order
Macrophage Activation
Matrix Metalloproteinase 9
Interleukin-12
Tumor Biomarkers
Fluorescent Antibody Technique
Publications
Immunity
Labels

ASJC Scopus subject areas

  • Dermatology
  • Molecular Biology
  • Cell Biology
  • Biochemistry

Cite this

Pettersen, J. S., Fuentes-Duculan, J., Suárez-Fariñas, M., Pierson, K. C., Pitts-Kiefer, A., Fan, L., ... Carucci, J. A. (Accepted/In press). Tumor-Associated Macrophages in the Cutaneous SCC Microenvironment Are Heterogeneously Activated. Journal of Investigative Dermatology. https://doi.org/10.103/jid.2011.9

Tumor-Associated Macrophages in the Cutaneous SCC Microenvironment Are Heterogeneously Activated. / Pettersen, Julia S.; Fuentes-Duculan, Judilyn; Suárez-Fariñas, Mayte; Pierson, Katherine C.; Pitts-Kiefer, Alexander; Fan, Linda; Belkin, Daniel A.; Wang, Claire Q F; Bhuvanendran, Shivaprasad; Johnson-Huang, Leanne M.; Bluth, Mark J.; Krueger, James G.; Lowes, Michelle A.; Carucci, John A.

In: Journal of Investigative Dermatology, 10.02.2011.

Research output: Contribution to journalArticle

Pettersen, JS, Fuentes-Duculan, J, Suárez-Fariñas, M, Pierson, KC, Pitts-Kiefer, A, Fan, L, Belkin, DA, Wang, CQF, Bhuvanendran, S, Johnson-Huang, LM, Bluth, MJ, Krueger, JG, Lowes, MA & Carucci, JA 2011, 'Tumor-Associated Macrophages in the Cutaneous SCC Microenvironment Are Heterogeneously Activated', Journal of Investigative Dermatology. https://doi.org/10.103/jid.2011.9
Pettersen JS, Fuentes-Duculan J, Suárez-Fariñas M, Pierson KC, Pitts-Kiefer A, Fan L et al. Tumor-Associated Macrophages in the Cutaneous SCC Microenvironment Are Heterogeneously Activated. Journal of Investigative Dermatology. 2011 Feb 10. https://doi.org/10.103/jid.2011.9
Pettersen, Julia S. ; Fuentes-Duculan, Judilyn ; Suárez-Fariñas, Mayte ; Pierson, Katherine C. ; Pitts-Kiefer, Alexander ; Fan, Linda ; Belkin, Daniel A. ; Wang, Claire Q F ; Bhuvanendran, Shivaprasad ; Johnson-Huang, Leanne M. ; Bluth, Mark J. ; Krueger, James G. ; Lowes, Michelle A. ; Carucci, John A. / Tumor-Associated Macrophages in the Cutaneous SCC Microenvironment Are Heterogeneously Activated. In: Journal of Investigative Dermatology. 2011.
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AU - Pitts-Kiefer, Alexander

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AU - Belkin, Daniel A.

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