期刊
CANCER SCIENCE
卷 107, 期 9, 页码 1206-1214出版社
WILEY
DOI: 10.1111/cas.13005
关键词
CD30; IL-17; IL-1 beta; neutrophil; gamma delta T cell
类别
资金
- MEXT
- Tokyo Biochemical Research Foundation (TBRF)
- [26430158]
- Grants-in-Aid for Scientific Research [26430158, 15J11569, 15K07947, 26670023, 15H05787, 15K08433, 26290059] Funding Source: KAKEN
Although it has been suspected that inflammation is associated with increased tumor metastasis, the exact type of immune response required to initiate cancer progression and metastasis remains unknown. In this study, by using an in vivo tumor progression model in which low tumorigenic cancer cells acquire malignant metastatic phenotype after exposure to inflammation, we found that IL-17A is a critical cue for escalating cancer cell malignancy. We further demonstrated that the length of exposure to an inflammatory microenvironment could be associated with acquiring greater tumorigenicity and that IL-17A was critical for amplifying such local inflammation, as observed in the production of IL-1 beta and neutrophil infiltration following the cross-talk between cancer and host stromal cells. We further determined that gamma delta T cells expressing V delta 1 semi-invariant TCR initiate cancer-promoting inflammation by producing IL-17A in an MyD88/IL-23-dependent manner. Finally, we identified CD30 as a key molecule in the inflammatory function of V delta 1T cells and the blockade of this pathway targeted this cancer immune-escalation process. Collectively, these results reveal the importance of IL-17A-producing CD30(+) V delta 1T cells in triggering inflammation and orchestrating a microenvironment leading to cancer progression.
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