COMBINING THERAPY OF DECITABINE PLUS POLY I:C TO IMPROVE ANTI-TUMOR RESPONSE IN BREAST CANCER

MARIBEL NICOLA; MARIANA MACCIONI; GERARDO GATTI

SAN MIGUEL DE TUCUMAN

Congreso; LVXII REUNIÓN CIENTÍFICA ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2019

SOCIEDAD ARGENTINA DE INMUNOLOGÍA

Molecular alterations impact tumor prognosis and response to treatment. Differential gene expression and DNA methylation signatures are seen in both primary and secondary breast cancer, including genes that are relevant to tumor growth and proliferation. The interferon regulatory factor-8 (IRF-8) is crucial for regulating the antitumor immune response trough type I interferons activation, and acts as a tumor suppressor gene. Results from our group showed that transcriptional silencing of IRF8 by DNA methylation correlates with the metastatic phenotype in breast cancer. In a breast cancer model, we observed an inhibition of tumor growth and tumor volume after local injection of Decitabine (demethylating agent) alone or combined with poly I:C compared to control. The aim of this works was to see if treatment with DAC could reinforce the activation of type I IFN signaling by poly I:C in breast cancer. 4T1 and MDA231 cells were treated with DAC alone or in combination with poly I:C. Then, we analyzed the gene expression related to type I IFN signaling. Breast cancer cells treated with DAC induced the expression of IFR3, IRF7, IFNB, CXCL10, RIG1 and MDA5. Treatment with DAC/poly I:C caused up-regulation of IFNB at significantly higher levels, compared with those receiving DAC or poly I:C alone (p