Profiles of expression of IL-17 receptor subunits in cancer cells dictate responsiveness to IL-17A.. Mus musculus

Stimulation of different tumor lines with IL-17A determined that IL-17 receptor expression patterns were associated with a different response according to tumor type. Mesenchymal cells (B16) expressing all three receptors showed a "classical" response to IL-17, which included increased mediators that are known targets of IL-17A such as GM-CSF, SAA3 and CXCL1 and the pro-inflammatory mediators VEGF and HIF1a. In contrast, hematopoietic cells EL4, showed a "non-classical" IL-17 response as they did not increase levels of typical post-stimulus pathway mediators and, particularly, EL4 increased levels of the immunoregulatory molecule PDL1. To perform a deeper analysis of the differences in response to IL-17 we evaluated at the transcriptional level the cellular processes enriched in B16 and EL4 after 24h of IL-17A stimulation and determined that IL-17A stimulates cellular processes related to the stimulation of the immune response and inflammation in B16 cells and, in contrast, cancer-related processes are enriched in EL4 cells.