Abstract
Chronic inflammation predisposes tissue to cancer development; however, regulatory mechanisms underlying recruitment of innate leukocytes toward developing neoplasms are obscure. We report that genetic elimination of mature T and B lymphocytes in a transgenic mouse model of inflammation-associated de novo epithelial carcinogenesis, e.g., K14-HPV16 mice, limits neoplastic progression to development of epithelial hyperplasias that fail to recruit innate immune cells. Adoptive transfer of B lymphocytes or serum from HPV16 mice into T and B cell-deficient/HPV16 mice restores innate immune cell infiltration into premalignant tissue and reinstates necessary parameters for full malignancy, e.g., chronic inflammation, angiogenic vasculature, hyperproliferative epidermis. These findings support a model in which B lymphocytes are required for establishing chronic inflammatory states that promote de novo carcinogenesis.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adoptive Transfer
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Animals
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B-Lymphocytes / cytology
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B-Lymphocytes / immunology*
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B-Lymphocytes / transplantation
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Blood Component Transfusion
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CD4 Antigens / genetics
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CD8 Antigens / genetics
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Carcinoma, Squamous Cell / etiology
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Carcinoma, Squamous Cell / immunology
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Carcinoma, Squamous Cell / pathology
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Cell Movement / immunology
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Cell Proliferation
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Chronic Disease
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Disease Models, Animal
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Gelatinases / metabolism
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Granulocytes / cytology
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Granulocytes / immunology
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Homeodomain Proteins / genetics
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Immunoglobulins / immunology
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Immunoglobulins / metabolism
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Inflammation / complications*
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Inflammation / immunology
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Keratinocytes / cytology
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Mast Cells / cytology
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Mast Cells / immunology
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Mice
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Mice, Knockout
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Mice, Transgenic
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Neoplasms, Glandular and Epithelial / etiology*
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Neoplasms, Glandular and Epithelial / immunology
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Neoplasms, Glandular and Epithelial / pathology
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Papillomaviridae / genetics
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Skin / cytology
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Skin / immunology
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Vascular Endothelial Growth Factor A / metabolism
Substances
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CD4 Antigens
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CD8 Antigens
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Homeodomain Proteins
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Immunoglobulins
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Vascular Endothelial Growth Factor A
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vascular endothelial growth factor A, mouse
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RAG-1 protein
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Gelatinases