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J Invest Dermatol ; 127(10): 2391-8, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17508019

ABSTRACT

Basal cell carcinoma (BCC), the most common human cancer, undergoes spontaneous regression in certain circumstances, which is potentially immune-mediated. To understand the immune response surrounding BCCs, we characterized the genomic, protein, and cellular microenvironment associated with BCC in comparison to normal skin. Our results demonstrated the following: (1) CD4+ CD25+ Foxp3+ surround epithelial tumor aggregates; (2) Immature dendritic cells (DCs) were abundant in the tumor microenvironment; (3) BCC showed increased expression of IL-4, IL-10, and CCL22 and increased expression of interferon-associated genes (IFI27, IRF1, IRF7, and G1P2) and IL-12/23, gene indicating a Th2 dominant microenvironment. Our findings suggest a dynamic state within the immune microenvironment associated with BCC. The finding of phenotypic T regs, in conjunction with immature DCs and Th2 cytokines, suggests an attenuated state of immunity to human BCC. In contrast, abundant CD8+ T cells, an interferon signal, and IL-12/23 suggest partial host antitumor response. A better understanding of these opposing forces within the immune microenvironment may facilitate development of more potent immune-based treatment for BCC and other human carcinomas.


Subject(s)
Carcinoma, Basal Cell/pathology , Forkhead Transcription Factors/metabolism , Skin Neoplasms/pathology , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Th2 Cells/pathology , Biopsy , CD4-Positive T-Lymphocytes/metabolism , CD4-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/pathology , Carcinoma, Basal Cell/immunology , Dendritic Cells/immunology , Dendritic Cells/pathology , Humans , Interferon Regulatory Factor-1/metabolism , Interferon Regulatory Factor-7/metabolism , Interleukin-10/metabolism , Interleukin-12/metabolism , Interleukin-4/metabolism , Skin Neoplasms/immunology , T-Lymphocytes, Regulatory/pathology , Th2 Cells/immunology
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