Demonstration of inflammation-induced cancer and cancer immunoediting during primary tumorigenesis

Jeremy B. Swann, Matthew D. Vesely, Anabel Silva, Janelle Sharkey, Shizuo Akira, Robert D. Schreiber, Mark J. Smyth

Research output: Contribution to journalArticlepeer-review

271 Scopus citations


Here we report the effects of loss of the Toll-like receptor-associated signaling adaptor myeloid-differentiation factor 88 (MyD88) on tumor induction in two distinct mouse models of carcinogenesis. The 7,12-dimethylbenz[a] anthracene (DMBA)/12-O-tetradecanoylphorbol 13-acetate (TPA)-induced skin papilloma model depends on proinflammatory processes, whereas the 3′-methylcholanthrene (MCA) induction of fibrosarcoma has been used by tumor immunologists to illustrate innate and adaptive immune surveillance of cancer. When exposed to a combination of DMBA/TPA, mice lacking MyD88 formed fewer skin papillomas than genetically matched WT controls treated in a similar manner. Unexpectedly, however, fewer MyD88-/- mice formed sarcomas than WT controls when exposed to MCA. In contrast, MyD88-deficient mice did not show a defective ability to reject highly immunogenic transplanted tumors, including MCA sarcomas. Despite the reported role of TNF in chronic inflammation, TNF-deficient mice were significantly more susceptible to MCA-induced sarcoma than WT mice. Overall, these data not only confirm the key role that MyD88 plays in promoting tumor development but also demonstrate that inflammation-induced carcinogenesis and cancer immunoediting can indeed occur in the same mouse tumor model.

Original languageEnglish
Pages (from-to)652-656
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number2
StatePublished - Jan 15 2008


  • Immunity
  • Surveillance


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