Oral Presentation 14th International Biennial Conference on Metastasis Research 2012

  Cancer immune-escalation process and the role of inflammatory tumor microenvironment for promoting metastasis (#41)

Yoshihiro Hayakawa 1 2 , Yoshitaka Kimura 2 , Naoki Tsunekawa 2 , Marimo Sato-Matsushita 3 , Hideaki Tahara 3 , Ikuo Saiki 1 , Tatsuro Irimura 2
  1. Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama, Japan
  2. Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
  3. Department of Surgery and Bioengineering, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan

Mounting evidences strongly supports the existence of an effective cancer immune surveillance process that prevents cancer development in both mouse and humans. It has been demonstrated that the importance of anti-cancer innate and adoptive effector cells and their anti-cancer effector molecules in the cancer immune-editing process. In addition to such positive role of immune responses, the indications of a possible link between inflammation and cancer has been extended in the last decade that the immune responses may play a positive role at different stage of tumor development including carcinogenesis process, malignant progression and disseminating metastasis. Although an inflammatory microenvironment is recognized as an essential component of all tumors, the precise mechanism remains to be clarified by which type of immune response can promote cancer disease in such microenvironment. In the present study, we have studied inflammatory immune responses and the role of cytokines in malignant progression of cancer. To examine the regulatory mechanism of host inflammatory responses in cancer malignant progression, we employ a very unique in vivo mouse model in which low tumorigenic original cancer cells acquire highly malignant metastatic phenotype after exposure to host inflammatory microenvironment. By using this unique in vivo cancer progression model combined with gene-targeted knockout mice, we examined the role of inflammatory mediators, specifically IFN-γ and IL-17, in the process of inflammation -associated cancer malignant progression. We have also characterized the precise immunological tumor microenvironment by which pre-malignant cells progress into malignant metastatic tumor cells, and found that a critical contribution of distinct inflammatory type γδ T cells in this immune-escalation process by producing IL-17. We would like to further discuss the potential of inflammatory IL-17-producing γδ T cells as a conductor of subsequent chronic inflammatory responses to orchestrate pro-tumor immunological microenvironment.