Immunotherapy against breast cancer based on Stat3 blockade

DE MARTINO, MARA; MERCOGLIANO, MARÍA FLORENCIA; TKACH, MERCEDES; VENTURUTTI, LEANDRO; PROIETTI, CECILIA J.; IZZO, FRANCO; ELIZALDE, PATRICIA V.; SCHILLACI, ROXANA

Mar del Plata

Congreso; LIX Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica; 2014

Sociedad Argentina de Inmunología (SAI)

IntroductionThe signal transducer and activator of transcription 3 (Stat3) is constitutively active in breast cancer (BC) and contributes to malignant transformation by promoting cell cycle progression, inhibiting apoptosis and mediating tumor immune evasion (1,2). Also Stat3 inhibition induces expression of proinflammatory cytokines and chemokines (3). Our laboratory has recently described that immunization of Balb/C mice with Stat3 blocked cells induces and antitumor immune response that involves the participation of CD4+ Th cells and cytotoxic NK cells (4). Interestingly, we observed that Stat3 blockage leads to a senescence program caused by oncogene inactivation (5) and accompanied by the secretion of pro-inflammatory cytokines.ObjectiveTo study the potential application of supernatants (SN) produced by Stat3 blocked breast cancer cells in immunotherapy and the role of senescence in this phenotype.ResultsFig.1Preclinical model of an immunotherapy protocol based on the administration of supernatant of Stat3 blocked cellsSA-β-gal staining was performed in C4HD cells transfected with Control siRNA, Stat3 siRNA or a combination of Stat3 and p16 siRNA. Female Balb/C mice were s.c. inyected with 1x106 irradiated C4HD cells together with a depot of SN of C4HD cells transfected either with Control siRNA, Stat3 siRNA or Stat3 and p16 siRNA. After 3 immunizations animals were challenged with C4HD tumor. Tumor growth was monitored by length and width measure. At day 40, splenocytes were obtained and NK cells activation, degranulation and memory CD4+ T cells were studied by flow cytometry. *P