De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent.
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.
de Visser
Karin E
KE
Cancer Research Institute, University of California, San Francisco, California 94143, USA.
Korets
Lidiya V
LV
Coussens
Lisa M
LM
D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D016913:Blood Component Transfusion; D015704:CD4 Antigens / Q000235:genetics; D016827:CD8 Antigens / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000276:immunology / Q000473:pathology; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D002908:Chronic Disease; D004195:Disease Models, Animal; D018093:Gelatinases / Q000378:metabolism; D006098:Granulocytes / Q000166:cytology / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics; D007136:Immunoglobulins / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000150:complications* / Q000276:immunology; D015603:Keratinocytes / Q000166:cytology; D008407:Mast Cells / Q000166:cytology / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009375:Neoplasms, Glandular and Epithelial / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D027383:Papillomaviridae / Q000235:genetics; D012867:Skin / Q000166:cytology / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D015704:CD4 Antigens; D016827:CD8 Antigens; D018398:Homeodomain Proteins; D007136:Immunoglobulins; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C064658:RAG-1 protein; D018093:Gelatinases