Human basal cell carcinoma is associated with Foxp3+ T cells in a Th2 dominant microenvironment

J Invest Dermatol. 2007 Oct;127(10):2391-8. doi: 10.1038/sj.jid.5700884. Epub 2007 May 17.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Carcinoma, Basal Cell / pathology*
  • Dendritic Cells / immunology
  • Dendritic Cells / pathology
  • Forkhead Transcription Factors / metabolism*
  • Humans
  • Interferon Regulatory Factor-1 / metabolism
  • Interferon Regulatory Factor-7 / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-12 / metabolism
  • Interleukin-4 / metabolism
  • Skin Neoplasms / immunology
  • Skin Neoplasms / pathology*
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism*
  • T-Lymphocytes, Regulatory / pathology
  • Th2 Cells / immunology
  • Th2 Cells / pathology*


  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IRF1 protein, human
  • IRF7 protein, human
  • Interferon Regulatory Factor-1
  • Interferon Regulatory Factor-7
  • Interleukin-10
  • Interleukin-12
  • Interleukin-4