Human Basal Cell Carcinoma Is Associated with Foxp3 super(+) T cells in a Th2 Dominant Microenvironment

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 c...

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Published inJournal of investigative dermatology Vol. 127; no. 10; pp. 2391 - 2398
Main Authors Kaporis, Helen G, Guttman-Yassky, Emma, Lowes, Michelle A, Haider, Asifa S, Fuentes-Duculan, Judilyn, Darabi, Kamruz, Whynot-Ertelt, Julia, Khatcherian, Artemis, Cardinale, Irma, Novitskaya, Inna, Krueger, James G, Carucci, John A
Format Journal Article
LanguageEnglish
Published 01.10.2007
Subjects
Antitumor activity
Basal cells
Carcinoma
CCL22 protein
CD8 antigen
Dendritic cells
Dermatology
Foxp3 protein
genomics
Helper cells
Interferon regulatory factor 1
Interferon regulatory factor 7
Interleukin 10
Interleukin 12
Interleukin 4
Internet
Lymphocytes T
Microenvironments
Skin
Tumors
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Summary: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 super(+)CD25 super(+)Foxp 3 super(+) 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 super(+) 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.Journal of Investigative Dermatology (2007) 127, 2391-2398; doi:10.1038/sj.jid.5700884; published online 17 May 2007
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ISSN:0022-202X
DOI:10.1038/sj.jid.5700884