B regulatory cells and the tumor-promoting actions of TNF-α during squamous carcinogenesis

• DOI: 10.1073/pnas.1100994108
• Publication Date: 2011-06-14T18:03:48Z
• Authors: Tiziana Schioppa; Robert Moore; Richard G. Thompson; Elizabeth C. Rosser; Hagen Kulbe; Sergei Nedospasov; Claudia Mauri; Lisa M. Coussens; Frances R. Balkwill
• Keywords: Adoptive Cell Transfer

The inflammatory cytokine TNF-α has been recognized as a critical tumor promoter, but the effector cells that mediate its action have not fully characterized. Because B regulate squamous and prostate carcinogenesis, Tnf −/− mice harbor B-cell defects, we investigated hypothesis are important for TNF-α–mediated promotion of cancer development. Using an adoptive transfer strategy 7,12-dimethylbenz[α]anthracene/terephthalic acid (DMBA/TPA) two-stage model skin found both development DMBA/TPA-induced papilloma. Transfer from DMBA/TPA-treated wild-type to rescued papilloma level, result observed when were transferred Rag2 or was eliminated selectively in cells. Resistance associated with increased IFN-γ CD8 + T significant reduction IL-10–producing regulatory alongside increase IFN-γ–producing spleen. These data indicate during carcinogenesis mediates tumor-promoting activity via repress antitumor immunity.