CD200 upregulation in vascular endothelium surrounding cutaneous squamous cell carcinoma.

Abstract

OBJECTIVE:

To characterize the presence of CD200 and CD200 receptor (CD200R) in the human cutaneous squamous cell carcinoma (SCC) microenvironment and to define a possible role for the CD200 axis in immune evasion by SCC.

DESIGN:

Gene expression in SCC vs normal skin was studied. Laser capture microdissection was used to determine differential expression of CD200 in normal skin vs actinic keratosis vs SCC in situ vs invasive SCC. Immunofluorescence microscopy was used to define expression of CD200R on macrophages, myeloid dendritic cells, natural killer cells, and T cells in SCC vs normal skin. The effects of SCC supernatant on induction of CD200 in human blood endothelial cells was also examined.

SETTING:

Academic Medical Center with an established Section of Mohs and Dermatologic Surgery and an active Cutaneous Biology Research Program.

PARTICIPANTS:

Surgical discard tissue from deidentified patients and samples of normal skin from healthy volunteers were used in this study.

MAIN OUTCOME MEASURES:

Expression of CD200 on SCC-associated blood vessels; expression of CD200 receptor on SCC-associated macrophages and T cells; and induction of CD200 on endothelial cells by SCC supernatants.

RESULTS:

CD200 gene and message were upregulated in SCC stroma. Immunostaining revealed a higher number of CD200(+) cells in SCC stroma than in normal dermis (180.8 cells/mm(2) vs 24.6 cells/mm(2)) (P<.01). CD200 was further identified mainly on blood vessel endothelium in SCC. Tumor supernatant was able to induce CD200 expression on human dermal blood endothelial cells in culture. CD200R was identified on macrophages and dendritic cells in SCC microenvironment.

CONCLUSIONS:

CD200 expression on local blood vessels may promote tumor progression by suppressing CD200R myeloid cells during diapedesis. These data highlight a previously unrecognized mechanism of immune evasion by SCC and may provide guidance for the development of targeted therapy.

• Authors: Daniel A Belkin, Hiroshi Mitsui, Claire Q F Wang, Juana Gonzalez, Shali Zhang, Kejal R Shah, Israel Coats, Mayte Suàrez-Fariñas, James G Krueger, Diane Felsen, John A Carucci
• Journal: JAMA dermatology (JAMA Dermatol) Vol. 149 Issue 2 Pg. 178-86 (Feb 2013) ISSN: 2168-6084 [Electronic] United States
• PMID: 23560298 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Antigens, Surface
• CD200R1 protein, human
• Orexin Receptors
• Receptors, Cell Surface
• antigens, CD200

Topics

• Academic Medical Centers
• Antigens, CD (genetics)
• Antigens, Surface (genetics)
• Carcinoma, Squamous Cell (genetics, immunology, pathology)
• Dendritic Cells (metabolism)
• Endothelium, Vascular (metabolism)
• Gene Expression Regulation, Neoplastic
• Humans
• Killer Cells, Natural (metabolism)
• Laser Capture Microdissection
• Macrophages (metabolism)
• Microscopy, Fluorescence
• Mohs Surgery
• Orexin Receptors
• Receptors, Cell Surface (genetics)
• Skin (metabolism)
• Skin Neoplasms (genetics, immunology, pathology)
• T-Lymphocytes (metabolism)
• Transendothelial and Transepithelial Migration
• Tumor Microenvironment
• Up-Regulation