Synergistic antitumor effect of anti-PD-1 with an immunotherapy based on STAT3 blockade

DE MARTINO, MARA; TKACH, MERCEDES; MERCOGLIANO, MARÍA FLORENCIA; CHERVO, MARÍA FLORENCIA; PROIETTI, CECILIA JAZMÍN; ELIZALDE, PATRICIA V.; PIAGGIO, ELIANE ; SCHILLACI, ROXANA

CABA

Congreso; Reunión conjunta de sociedades de biociencias, LXII Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2017

Sociedad Argentina de Investigación Clínica (SAIC)

Stat3 is constitutively activated in diverse cancers and acts as a critical mediator of tumor immune evasion. We described in murine breast cancer (BC) models, that blockade of Stat3 activationinduces senescence and that immunization of mice with irradiated Stat3-blocked BC cells inhibits tumor growth. Our objectives were to study the secretome induced by Stat3 blockade and to develop an immunotherapy (IT) based on the supernatant (SN) from Stat3-blocked cells. We observed that knockdown of Stat3 with siRNA increased senescence 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) or Stat3 siRNA (SN-Stat3) as an adjuvant of a cellular vaccine with irradiated wild-type tumor cells. Therapeutic IT with SN-Stat3 in mice bearing 4T1 or B16-OVA tumors decreased tumor growth (51%, p