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

C RODRIGUEZ; C ARAUJO FURLAN; S BOSSIO; S BOCCARDO; J TOSELLO BOARI; D CESCHIN; E PIAGGIO; A GRUPPI; C MONTES; E ACOSTA RODRÍGUEZ

Congreso; Reunión de Sociedades de Biociencias 2021; 2021

SAIC - SAI - AAFE - NANOMED-AR

The role of IL-17 signaling in tumor progression is discussed as itsustains, directly and indirectly, tumor growth and immune-escapebut also supports anti-tumoral immunity by boosting CD8+ T and NKcell responses. Our aim is to determine the role of IL-17 signalingin tumor progression dissecting pro- and anti-tumoral effects. Forthis, we used B16 (melanoma) and EL4 (thymoma) cells that accordingto previous results show a different IL-17 receptor (IL-17R)expression profile:both expressed IL-17RA and IL-17RD whereasonly B16 cells expressed IL-17RC. In addition, B16 and EL4 exhibiteddivergent tumor growth in hosts deficient in IL-17 signaling.These data led us to hypothesize that IL-17 may trigger differenttranscriptional programs in both cell lines to promote or restrain tumorprogression. To evaluate this, we performed RNA-seq to comparethe transcriptomes and differentially expressed genes (DEG)in B16 and EL4 cells after exposure to IL-17 for 24h. We confirmedthe different IL-17R expression profiles in both cell lines that werelinked to significant differences in the expression of genes of theIL-17 pathway in the basal condition. Exposure to IL-17 led to differentoutcomes among the cell lines. Comparison of medium vsIL-17 treated cells revealed 374 DEG (179 up and 195 down) inB16 cells, and 535 DEGs (444 up and 96 down) in EL4 cells withonly 12 genes in common (6up, 5down and 1 with opposite result)(p<0.05, logFC>1.5). Ingenuity Pathway Analysis highlighted withinthe Top Canonical Pathways enriched in IL-17-treated B16 cellspathways associated to cytokine-mediated responses while withinthose enriched in IL-17-treated EL4 cells predominated pathwaysassociated to signaling during cellular processes such as cell growthand cell-to-cell interactions. Our results highlight that IL-17-signalingtriggered diverse responses in different tumor cells that may modulatetumor growth likely as consequence of particular profiles ofIL-17R subunit expression.