FcRγ Activation Regulates Inflammation-Associated Squamous Carcinogenesis

Pauline Andreu, Magnus Johansson, Nesrine I. Affara, Ferdinando Pucci, Tingting Tan, Simon Junankar, Lidiya Korets, Julia Lam, David Tawfik, David G. DeNardo, Luigi Naldini, Karin E. de Visser, Michele De Palma, Lisa M. Coussens

Research output: Contribution to journalArticle

332 Scopus citations

Abstract

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 Fcγ receptors (FcγRs) on resident and recruited myeloid cells. Stromal accumulation of autoantibodies in premalignant skin, through their interaction with activating FcγRs, 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 FcγRs are required for establishing chronic inflammatory programs that promote de novo carcinogenesis.

Original languageEnglish (US)
Pages (from-to)121-134
Number of pages14
JournalCancer Cell
Volume17
Issue number2
DOIs
StatePublished - Feb 17 2010

Keywords

  • CELLCYCLE
  • CELLIMMUNO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Andreu, P., Johansson, M., Affara, N. I., Pucci, F., Tan, T., Junankar, S., Korets, L., Lam, J., Tawfik, D., DeNardo, D. G., Naldini, L., de Visser, K. E., De Palma, M., & Coussens, L. M. (2010). FcRγ Activation Regulates Inflammation-Associated Squamous Carcinogenesis. Cancer Cell, 17(2), 121-134. https://doi.org/10.1016/j.ccr.2009.12.019