IL‐17A‐producing CD30+ Vδ1 T cells drive inflammation‐induced cancer progression. Issue 9 (1st September 2016)

• Record Type: Journal Article
• Authors: Kimura, Yoshitaka; Nagai, Nao; Tsunekawa, Naoki; Sato‐Matsushita, Marimo; Yoshimoto, Takayuki; Cua, Daniel J.; Iwakura, Yoichiro; Yagita, Hideo; Okada, Futoshi; Tahara, Hideaki; Saiki, Ikuo; Irimura, Tatsuro; Hayakawa, Yoshihiro
• Is Part Of: Cancer science. Volume 107:Issue 9(2016)
• Page Start: 1206
• Page End: 1214
• Publication Date: 2016-09-01
• Subjects: CD30 -- IL‐17 -- IL‐1β -- neutrophil -- γδ T cell; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.13005
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract : 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‐1β and neutrophil infiltration following the cross‐talk between cancer and host stromal cells. We further determined that γδT cells expressing Vδ1 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 Vδ1T cells and the blockade of this pathway targeted this cancer immune‐escalation process. Collectively, these results reveal the importance of IL‐17A‐producing CD30 + Vδ1T cells in triggering inflammation and orchestrating a microenvironment leading to cancer progression. Abstract : Our presented results reveal the importance of IL‐17A‐producing CD30+ Vδ1T cells in triggering inflammation and orchestrating a microenvironment leading to cancer progression.