Human basal cell carcinoma is associated with Foxp3+ 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 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.
Kaporis
Helen G
HG
Laboratory for Investigative Dermatology, Rockefeller University, New York, New York, USA.
Guttman-Yassky
Emma
E
Lowes
Michelle A
MA
Haider
Asifa S
AS
Fuentes-Duculan
Judilyn
J
Darabi
Kamruz
K
Whynot-Ertelt
Julia
J
Khatcherian
Artemis
A
Cardinale
Irma
I
Novitskaya
Inna
I
Krueger
James G
JG
Carucci
John A
JA
D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002280:Basal Cell Carcinoma / Q000276:immunology / Q000473:pathology*; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism; D050839:Interferon Regulatory Factor-7 / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C494257:IRF1 protein, human; C494234:IRF7 protein, human; D050856:Interferon Regulatory Factor-1; D050839:Interferon Regulatory Factor-7; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4