Study of the IL-17 family cytokines and receptors expression on different tumor cell lines and their impact on tumor progression

C RODRIGUEZ; J TOSELLO BOARI; C ARAUJO FURLAN; F CANALE; S BOCCARDO; S BOSSIO; CG BECCARIA; A GRUPPI; CL MONTES; EV ACOSTA RODRIGUEZ

Mar del Plata

Congreso; LXVI Reunión Anual de la Sociedad Argentina de Inmunología; 2018

Sociedad Argentina de Inmunología

While relatively well-defined in infectious diseases and autoimmunity,the roles of IL-17 cytokines in cancer remain controversial. Thus,IL-17 may play a pro-tumoral role by directly sustaining cancer cellgrowth or may support antitumoral immunity potentiating CD8+ Tcell (CTL) and NK cell responses. Our aim is to determine the roleof IL-17 in the overall progression of different cancer types, dissectingpro-tumoral and anti-tumoral effects. Using different murinetumor cell lines of melanoma (B16-SIY), fibrosarcoma (MC57-SIYand MCA-OVA), lymphoma (EL4-SIY) and acute myeloid leukemia(C1498-SIY), we first quantified by real-time PCR the transcripts encodingIL-17A and IL-17F and receptors subunits IL-17RA, IL-17RCand IL-17RD. IL-17A transcript was detected only in EL4-SIY whileIL-17RA, IL-17RD and IL-17F mRNA were expressed in all the celllines assayed. IL-17RC transcripts were expressed in MCA-OVA,B16-SIY and MC57-SIY but not in EL4-SIY nor in C1498-SIY. Importantvariations in transcript amounts were observed among celllines evaluated: IL-17F mRNA expression was higher in C1498-SIY(p< 0.001) and B16-SIY (p<0.05); IL-17RC mRNA augmented inB16-SIY (p<0.001) and MCA-OVA (p<0.05); IL-17RA and IL-17RDtranscripts were augmented in B16-SIY (p<0.01 and p<0.001, respectively).These differences suggest dissimilar sensitivities of thecell lines to IL-17-mediated growth signals. We next investigatedtumor progression and antitumoral immunity after injection of cellsin WT (B6) mice in comparison to mice deficient in IL-17RA (RKO)or IL-17A and IL-17F (DKO). Injection of B16-SIY and MC57-SIYin RKO and DKO mice resulted in increased tumor volume and reducedtumor-specific CTL in comparison to WT mice while injectionof MCA-OVA showed no differences in tumor progression amongall experimental groups. These results indicate that IL-17 cytokineshave dissimilar impact in the overall progression of different tumors.Further research will establish the relative influence of pro- and anti-tumoral effects according to the cancer phenotype.