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Chemical carcinogens and antigens contribute to cutaneous tumor promotion by depleting epidermal Langerhans cells


Qu, MM and Muller, HK and Woods, GM, Chemical carcinogens and antigens contribute to cutaneous tumor promotion by depleting epidermal Langerhans cells, Carcinogenesis, 18, (6) pp. 1277-1279. ISSN 0143-3334 (1997) [Refereed Article]

DOI: doi:10.1093/carcin/18.6.1277


Epidermal Langerhans cells (LC) are an integral component of the skin immune system as they initiate immune responses to a variety of antigens, including tumor antigens. When skin is exposed to carcinogenic doses of ultraviolet-B irradiation, chemical carcinogens or tumor promoters there is a significant reduction of LC density. This causes the skin to be immunocompromised and provides an opportunity for aberrant cells to escape immune detection and develop into tumors. Consequently LC depletion is a key event associated with the pathogenesis of skin cancer. We propose that LC depletion contributes to tumor promotion and therefore any agents that reduce LC number, e.g. the contact sensitizing antigen 2,4,6-trinitrochlorobenzene (TNCB), may also contribute to tumor promotion. This proposal was evaluated in cutaneous carcinogenesis by treating mouse skin with a tumor initiating dose of the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) followed by a tumor promoter. The initiating dose of DMBA did not cause LC depletion or tumor development. However, if the DMBA-treated skin was then exposed to a concentration of TNCB that caused LC depletion, skin tumors developed. This is analogous to the classical initiator/ promoter system with an LC-depleting dose of TNCB contributing to tumor promotion. Further, this promotion effect was independent of the commencement time of the promoter application, as 2% TNCB applied either 1 or 12 weeks after DMBA initiation induced tumor development. Analysis of the association of LC depletion with immunosuppression and tumor promotion, showed that these events were linked, irrespective of the agent that caused the depletion. It is therefore concluded that LC depletion and local immunosuppression are important aspects of tumor promotion in cutaneous carcinogenesis and non-carcinogenic agents may have tumor promoter activities.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Immunology
Research Field:Tumour immunology
Objective Division:Health
Objective Group:Other health
Objective Field:Other health not elsewhere classified
UTAS Author:Qu, MM (Mrs Miao Qu)
UTAS Author:Muller, HK (Professor Konrad Muller)
UTAS Author:Woods, GM (Professor Gregory Woods)
ID Code:9597
Year Published:1997
Web of Science® Times Cited:16
Deposited By:Pathology
Deposited On:1997-08-01
Last Modified:2011-08-11

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