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B regulatory cells and the tumor-promoting actions of TNF-alpha during squamous carcinogenesisстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 18 июля 2013 г.
- Авторы: Schioppa Tiziana, Moore Robert, Thompson Richard G., Rosser Elizabeth C., Kulbe Hagen, Nedospasov Sergei, Mauri Claudia, Coussens Lisa M., Balkwill Frances R.
- Журнал: Proceedings of the National Academy of Sciences of the United States of America
- Том: 108
- Номер: 26
- Год издания: 2011
- Издательство: National Academy of Sciences
- Местоположение издательства: United States
- Первая страница: 10662
- Последняя страница: 10667
- DOI: 10.1073/pnas.1100994108
- Аннотация: 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[a] 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 observedwhen B cells from Tnf(-/-) mice were transferred to Rag2(-/-) mice or when TNF-alpha was eliminated selectively in B cells. Resistance to papilloma developmentin 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.
- Добавил в систему: Недоспасов Сергей Артурович
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