FcRgamma activation regulates inflammation-associated squamous carcinogenesis.
Chronically activated leukocytes recruited to premalignant tissues functionally contribute to cancer development; however, mechanisms underlying pro- versus anti-tumor programming of neoplastic tissues by immune cells remain obscure. Using the K14-HPV16 mouse model of squamous carcinogenesis, we report that B cells and humoral immunity foster cancer development by activating Fcgamma receptors (FcgammaRs) on resident and recruited myeloid cells. Stromal accumulation of autoantibodies in premalignant skin, through their interaction with activating FcgammaRs, regulate recruitment, composition, and bioeffector functions of leukocytes in neoplastic tissue, which in turn promote neoplastic progression and subsequent carcinoma development. These findings support a model in which B cells, humoral immunity, and activating FcgammaRs are required for establishing chronic inflammatory programs that promote de novo carcinogenesis.
Department of Pathology, University of California, San Francisco, 94143, USA.
Pauline
P
Andreu
Magnus
M
Johansson
Nesrine I
NI
Affara
Ferdinando
F
Pucci
Tingting
T
Tan
Simon
S
Junankar
Lidiya
L
Korets
Julia
J
Lam
David
D
Tawfik
David G
DG
DeNardo
Luigi
L
Naldini
Karin E
KE
de Visser
Michele
M
De Palma
Lisa M
LM
Coussens
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D056724:Immunity, Humoral / Q000502:physiology; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D009375:Neoplasms, Glandular and Epithelial / Q000098:blood supply / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic; D017452:Receptors, IgG / Q000378:metabolism / Q000502:physiology*
D039481:CD11b Antigen; D017452:Receptors, IgG