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.
Andreu
Pauline
P
Department of Pathology, University of California, San Francisco, 94143, USA.
Johansson
Magnus
M
Affara
Nesrine I
NI
Pucci
Ferdinando
F
Tan
Tingting
T
Junankar
Simon
S
Korets
Lidiya
L
Lam
Julia
J
Tawfik
David
D
DeNardo
David G
DG
Naldini
Luigi
L
de Visser
Karin E
KE
De Palma
Michele
M
Coussens
Lisa M
LM
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