FcRgamma activation regulates inflammation-associated squamous carcinogenesis

Cancer Cell. 2010 Feb 17;17(2):121-34. doi: 10.1016/j.ccr.2009.12.019. Epub 2010 Feb 4.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • CD11b Antigen / metabolism
  • Carcinoma, Squamous Cell / blood supply
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Immunity, Humoral / physiology
  • Mast Cells / immunology
  • Mast Cells / metabolism
  • Mast Cells / pathology
  • Mice
  • Mice, Transgenic
  • Models, Biological
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism
  • Neoplasms, Glandular and Epithelial / blood supply
  • Neoplasms, Glandular and Epithelial / immunology*
  • Neoplasms, Glandular and Epithelial / metabolism
  • Neoplasms, Glandular and Epithelial / pathology
  • Neovascularization, Pathologic
  • Receptors, IgG / metabolism
  • Receptors, IgG / physiology*


  • CD11b Antigen
  • Receptors, IgG