FcRγ 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 Bcells and humoral immunity foster cancer development by activating Fc gamma receptors (Fc gamma Rs) on resident and recruited myeloid cells. Stromal accumulation of autoantibodies in premalignant skin, through their interaction with activating Fc gamma Rs, 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 Fc gamma Rs are required for establishing chronic inflammatory programs that promote de novo carcinogenesis.