Immune enhancement of skin carcinogenesis by CD4+ T cells.
In a transgenic model of multi-stage squamous carcinogenesis induced by human papillomavirus (HPV) oncogenes, infiltrating CD4+ T cells can be detected in both premalignant and malignant lesions. The lymph nodes that drain sites of epidermal neoplasia contain activated CD4+ T cells predominantly reactive toward Staphylococcal bacterial antigens. HPV16 mice deficient in CD4+ T cells were found to have delayed neoplastic progression and a lower incidence of tumors. This delay in carcinogenesis is marked by decreased infiltration of neutrophils, and reduced activity of matrix metalloproteinase-9, an important cofactor for tumor progression in this model. The data reveal an unexpected capability of CD4 T cells, whereby, proinflammatory CD4+ T cells, apparently responding to bacterial infection of dysplastic skin lesions, can inadvertently enhance neoplastic progression to invasive cancer.
Daniel
Dylan
D
Department of Biochemistry and Biophysics, Diabetes and Comprehensive Cancer Centers, University of California at San Francisco, 94143, USA.
Meyer-Morse
Nicole
N
Bergsland
Emily K
EK
Dehne
Kerstin
K
Coussens
Lisa M
LM
Hanahan
Douglas
D
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D027383:Papillomaviridae / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013211:Staphylococcus aureus / Q000276:immunology / Q000378:metabolism; D013212:Staphylococcus epidermidis / Q000276:immunology / Q000378:metabolism
D000942:Antigens, Bacterial; D016177:Macrophage-1 Antigen; D007371:Interferon-gamma; D020780:Matrix Metalloproteinase 9