| First Author | Schioppa T | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 26 | Pages | 10662-7 |
| PubMed ID | 21670304 | Mgi Jnum | J:173541 |
| Mgi Id | MGI:5014433 | Doi | 10.1073/pnas.1100994108 |
| Citation | Schioppa T, et al. (2011) B regulatory cells and the tumor-promoting actions of TNF-{alpha} during squamous carcinogenesis. Proc Natl Acad Sci U S A 108(26):10662-7 |
| abstractText | The inflammatory cytokine TNF-alpha has been recognized as a critical tumor promoter, but the effector cells that mediate its action have not been fully characterized. Because B cells regulate squamous and prostate carcinogenesis, and Tnf(-/-) mice harbor B-cell defects, we investigated the hypothesis that B cells are important effector cells for TNF-alpha-mediated promotion of cancer development. Using an adoptive transfer strategy and the 7,12-dimethylbenz[alpha]anthracene/terephthalic acid (DMBA/TPA) two-stage model of skin carcinogenesis, we found that both B cells and TNF-alpha are critical for the development of DMBA/TPA-induced papilloma. Transfer of B cells from DMBA/TPA-treated wild-type mice to Tnf(-/-) mice rescued papilloma development to a wild-type level, a result not observed when B cells from Tnf(-/-) mice were transferred to Rag2(-/-) mice or when TNF-alpha was eliminated selectively in B cells. Resistance to papilloma development in Tnf(-/-) mice was associated with increased IFN-gamma and CD8(+) T cells in skin and a significant reduction in IL-10-producing B regulatory cells alongside an increase in IFN-gamma-producing CD8(+) T cells in the spleen. These data indicate that during DMBA/TPA-induced squamous carcinogenesis TNF-alpha mediates tumor-promoting activity via regulatory B cells that repress antitumor immunity. |
