TY - JOUR
T1 - Human basal cell carcinoma is associated with Foxp3+ T cells in a Th2 dominant microenvironment
AU - Kaporis, Helen G.
AU - Guttman-Yassky, Emma
AU - Lowes, Michelle A.
AU - Haider, Asifa S.
AU - Fuentes-Duculan, Judilyn
AU - Darabi, Kamruz
AU - Whynot-Ertelt, Julia
AU - Khatcherian, Artemis
AU - Cardinale, Irma
AU - Novitskaya, Inna
AU - Krueger, James G.
AU - Carucci, John A.
N1 - Funding Information:
This work was supported in part by the Dermatology Foundation.
PY - 2007/10
Y1 - 2007/10
N2 - 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.
AB - 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.
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U2 - 10.1038/sj.jid.5700884
DO - 10.1038/sj.jid.5700884
M3 - Article
C2 - 17508019
AN - SCOPUS:34848812857
SN - 0022-202X
VL - 127
SP - 2391
EP - 2398
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 10
ER -