IL-17A-producing CD30+ Vδ1 T cells drive inflammation-induced cancer progression

Summary

Although it has been suspected that inflammation associates with increased tumor metastasis, the exact type of immune response 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 IL-17A is a critical cue for escalating cancer cell malignancy. We further demonstrated the length of exposure to an inflammatory microenvironment could associate with acquiring greater tumorigenicity and 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.

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