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

Buenos Aires

Congreso; Reunión Conjunta de Ciencias Biomédicas; 2021

SAI - SAIC-SAB-AAFE-AACYTAL

The role of IL-17 signaling in tumor progression is controversial as it sustains, directly and indirectly, tumor growth and immune-escape but also supports anti-tumoral immunity by potentiating CD8+ T and NK cell responses. Our aim is to determine the role of IL-17 signaling in tumor progression dissecting pro- and anti-tumoral effects. For this, we used B16 (melanoma) and EL4 (thymoma) tumor cells that according to previous show a different IL-17 receptor (IL-17R) expression profile: both expressed IL-17RA and IL-17RD whereas only B16 cells expressed IL-17RC. This together with the fact that B16 and EL4 exhibited divergent tumor growth in hosts deficient in IL-17 signaling, led us to hypothesize that IL-17 may trigger different transcriptional programs in both cell lines to either promote or restrain tumor progression. To evaluate this, we perfomed RNA-seq to compare the transcriptomes and differentially expressed genes (DEG) in B16 and EL4 cells after exposure to IL-17 for 24h. We confirmed the different profiles of expression of IL-17R subunits in both cell lines that were associated with significant differences in the expression of additional genes of the IL-17 pathway in the basal condition. Of note, the exposure to IL-17A resulted in different outcomes in each cell line. Comparison of medium vs IL-17 trated cells revealed 374 DEG (179 up and 195 down) in B16 cells and 535 DEGs (444 up and 96 down) in EL4 cells with only 12 genes in common (6 up, 5 down and 1 with opposite response)(p<0.05, logFC>1.5). Ingenuity Pathway Analysis highlighted within the Top Canonical Pathways enriched in IL-17-stimulated B16 cells pathways associated to cytokine-mediated responses while within those enriched in IL-17-stimulated EL4 cells predominated pathways associated to signaling during cellular processes associated to cell growth and cell-to-cell interactions. Our results highlight that IL-17-signaling triggered diverse responses in different tumor cells that may divergently modulate tumor growth likely as consequence of particular profiles of IL-17R subunit expression.