In vitro stimulation with IL-17 induces distinctive responses in different tumor cell lines according to their IL-17R expression profile.

RODRIGUEZ C; ARAUJO FURLÁN CL; BOSSIO SN; BOCCARDO S; TOSELLO BOARI J; CESCHIN D; PIAGGIO E; GRUPPI A; MONTES CL; ACOSTA RODRIGUEZ EV

Congreso; Reunión Conjunta SAIC.SAI.AAFE.NANOMED.Ar.; 2021

The role of IL-17 signaling in tumor progression is discussed as it sustains, directly andindirectly, tumor growth and immune-escape but also supports anti-tumoral immunity byboosting CD8+ T and NK cell responses. Our aim is to determine the role of IL-17signaling in tumor progression dissecting pro- and anti-tumoral effects. For this, we usedB16 (melanoma) and EL4 (thymoma) cells that according to previous results show adifferent IL-17 receptor (IL-17R) expression profile:both expressed IL-17RA and IL-17RDwhereas only B16 cells expressed IL-17RC. In addition, B16 and EL4 exhibited divergenttumor growth in hosts deficient in IL-17 signaling. These data led us to hypothesize thatIL-17 may trigger different transcriptional programs in both cell lines to promote orrestrain tumor progression. To evaluate this, we performed RNA-seq to compare thetranscriptomes and differentially expressed genes (DEG) in B16 and EL4 cells afterexposure to IL-17 for 24h. We confirmed the different IL-17R expression profiles in bothcell lines that were linked to significant differences in the expression of genes of the IL-17 pathway in the basal condition. Exposure to IL-17 led to different outcomes amongthe cell lines. Comparison of medium vs IL-17 treated cells revealed 374 DEG (179 upand 195 down) in B16 cells, and 535 DEGs (444 up and 96 down) in EL4 cells with only12 genes in common (6up, 5down and 1 with opposite result) (p<0.05, logFC>1.5).Ingenuity Pathway Analysis highlighted within the Top Canonical Pathways enriched inIL-17-treated B16 cells pathways associated to cytokine-mediated responses whilewithin those enriched in IL-17-treated EL4 cells predominated pathways associated tosignaling during cellular processes such as cell growth and cell-to-cell interactions. Ourresults highlight that IL-17-signaling triggered diverse responses in different tumor cellsthat may modulate tumor growth likely as consequence of particular profiles of IL-17Rsubunit expression.