Myeloid dendritic cells from human cutaneous squamous cell carcinoma are poor stimulators of T-cell proliferation

Mark J. Bluth, Lisa C. Zaba, Dariush Moussai, Mayte Suárez-Farĩas, Helen Kaporis, Linda Fan, Katherine C. Pierson, Traci R. White, Alexander Pitts-Kiefer, Judilyn Fuentes-Duculan, Emma Guttman-Yassky, James G. Krueger, Michelle A. Lowes, John A. Carucci

Research output: Contribution to journalArticle

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Abstract

To determine the phenotype and function of myeloid dendritic cells (DCs) from human cutaneous squamous-cell carcinoma (SCC), we studied their surface marker expression and allo-stimulatory potential ex vivo. There were abundant CD11c myeloid DCs, as well as TNF and inducible nitric oxide synthase (iNOS)-producing DCs, in and around SCC tumor nests. Although myeloid DCs from SCC, adjacent non-tumor-bearing skin, and normal skin, were phenotypically similar by flow cytometry, and there was a pronounced genomic signature of mature DCs in SCC, they showed different T-cell stimulatory potential in an allogeneic mixed leukocyte reaction. Myeloid DCs from SCC were less potent stimulators of allogeneic T-cell proliferation than DCs from non-tumor-bearing skin. Culture with a DC-maturing cytokine cocktail (IL-1Β, IL-6, TNF-α, and PGE 2) enhanced stimulatory potential in DCs from non-tumor-bearing skin, whereas SCC-associated DCs remained poor stimulators of T-cell proliferation. The microenvironment associated with SCC showed expression of TGF-Β, IL-10, and VEGF-A, factors capable of suppressing the DC function. These findings indicate that CD11c /HLA-DR hi DCs from SCC are mature, but are not potent stimulators of T-cell proliferation compared with phenotypically similar DCs isolated from non-tumor-bearing skin. Identification of mechanisms responsible for suppression of tumor-associated DCs may provide insight into the evasion of immunosurveillance by SCC.

Original languageEnglish (US)
Pages (from-to)2451-2462
Number of pages12
JournalJournal of Investigative Dermatology
Volume129
Issue number10
DOIs
StatePublished - Oct 2009
Externally publishedYes

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T-cells
Cell proliferation
Myeloid Cells
Dendritic Cells
Squamous Cell Carcinoma
Cell Proliferation
T-Lymphocytes
Skin
Bearings (structural)
Epithelial Cells
Tumors
Immunologic Monitoring
Mixed Lymphocyte Culture Test
Flow cytometry
HLA-DR Antigens
Nitric Oxide Synthase Type II
Prostaglandins E
Interleukin-1
Interleukin-10
Vascular Endothelial Growth Factor A

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Bluth, M. J., Zaba, L. C., Moussai, D., Suárez-Farĩas, M., Kaporis, H., Fan, L., ... Carucci, J. A. (2009). Myeloid dendritic cells from human cutaneous squamous cell carcinoma are poor stimulators of T-cell proliferation. Journal of Investigative Dermatology, 129(10), 2451-2462. https://doi.org/10.1038/jid.2009.96

Myeloid dendritic cells from human cutaneous squamous cell carcinoma are poor stimulators of T-cell proliferation. / Bluth, Mark J.; Zaba, Lisa C.; Moussai, Dariush; Suárez-Farĩas, Mayte; Kaporis, Helen; Fan, Linda; Pierson, Katherine C.; White, Traci R.; Pitts-Kiefer, Alexander; Fuentes-Duculan, Judilyn; Guttman-Yassky, Emma; Krueger, James G.; Lowes, Michelle A.; Carucci, John A.

In: Journal of Investigative Dermatology, Vol. 129, No. 10, 10.2009, p. 2451-2462.

Research output: Contribution to journalArticle

Bluth, MJ, Zaba, LC, Moussai, D, Suárez-Farĩas, M, Kaporis, H, Fan, L, Pierson, KC, White, TR, Pitts-Kiefer, A, Fuentes-Duculan, J, Guttman-Yassky, E, Krueger, JG, Lowes, MA & Carucci, JA 2009, 'Myeloid dendritic cells from human cutaneous squamous cell carcinoma are poor stimulators of T-cell proliferation', Journal of Investigative Dermatology, vol. 129, no. 10, pp. 2451-2462. https://doi.org/10.1038/jid.2009.96
Bluth, Mark J. ; Zaba, Lisa C. ; Moussai, Dariush ; Suárez-Farĩas, Mayte ; Kaporis, Helen ; Fan, Linda ; Pierson, Katherine C. ; White, Traci R. ; Pitts-Kiefer, Alexander ; Fuentes-Duculan, Judilyn ; Guttman-Yassky, Emma ; Krueger, James G. ; Lowes, Michelle A. ; Carucci, John A. / Myeloid dendritic cells from human cutaneous squamous cell carcinoma are poor stimulators of T-cell proliferation. In: Journal of Investigative Dermatology. 2009 ; Vol. 129, No. 10. pp. 2451-2462.
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AU - Suárez-Farĩas, Mayte

AU - Kaporis, Helen

AU - Fan, Linda

AU - Pierson, Katherine C.

AU - White, Traci R.

AU - Pitts-Kiefer, Alexander

AU - Fuentes-Duculan, Judilyn

AU - Guttman-Yassky, Emma

AU - Krueger, James G.

AU - Lowes, Michelle A.

AU - Carucci, John A.

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N2 - To determine the phenotype and function of myeloid dendritic cells (DCs) from human cutaneous squamous-cell carcinoma (SCC), we studied their surface marker expression and allo-stimulatory potential ex vivo. There were abundant CD11c myeloid DCs, as well as TNF and inducible nitric oxide synthase (iNOS)-producing DCs, in and around SCC tumor nests. Although myeloid DCs from SCC, adjacent non-tumor-bearing skin, and normal skin, were phenotypically similar by flow cytometry, and there was a pronounced genomic signature of mature DCs in SCC, they showed different T-cell stimulatory potential in an allogeneic mixed leukocyte reaction. Myeloid DCs from SCC were less potent stimulators of allogeneic T-cell proliferation than DCs from non-tumor-bearing skin. Culture with a DC-maturing cytokine cocktail (IL-1Β, IL-6, TNF-α, and PGE 2) enhanced stimulatory potential in DCs from non-tumor-bearing skin, whereas SCC-associated DCs remained poor stimulators of T-cell proliferation. The microenvironment associated with SCC showed expression of TGF-Β, IL-10, and VEGF-A, factors capable of suppressing the DC function. These findings indicate that CD11c /HLA-DR hi DCs from SCC are mature, but are not potent stimulators of T-cell proliferation compared with phenotypically similar DCs isolated from non-tumor-bearing skin. Identification of mechanisms responsible for suppression of tumor-associated DCs may provide insight into the evasion of immunosurveillance by SCC.

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