Synergistic antitumor effect of anti-PD-1 with an immunotherapy based on Stat3 blockade.

PATRICIA VIRGINIA ELIZALDE; MARIA FLORENCIA MERCOGLIANO; ROXANA SCHILLACI; CECILIA JAZMÍN PROIETTI; MERCEDES TKACH; ELIANE PIAGGIO; MARÍA FLORENCIA CHERVO; MARA DE MARTINO

Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

Stat3 is constitutively activated in diverse cancers and acts as acritical mediator of tumor immune evasion. We described in murinebreast cancer (BC) models, that blockade of Stat3 activationinduces senescence and that immunization of mice with irradiatedStat3-blocked BC cells inhibits tumor growth. Our objectives were tostudy the secretome induced by Stat3 blockade and to develop animmunotherapy (IT) based on the supernatant (SN) from Stat3-blockedcells. We observed that knockdown of Stat3 with siRNA increasedsenescence markers in BC, colon cancer and melanoma models.Then, we used the serum-free SN from 4T1 (BC) or B16-OVA(melanoma) cells transfected with Control siRNA (SN-Control) orStat3 siRNA (SN-Stat3) as an adjuvant of a cellular vaccine withirradiated wild-type tumor cells. Therapeutic IT with SN-Stat3 in micebearing 4T1 or B16-OVA tumors decreased tumor growth (51%,p