Targeting Stat3 induces senescence in breast cancer cells and elicits an immune response inhibiting tumor growth and metastasis

MERCEDES TKACH; MARTIN RIVAS; CECILIA J. PROIETTI; DÍAZ FLAQUÉ, CELESTE; FRAHM, ISABEL; EDUARDO CHARREAU; ELIZALDE, PATRICIA V; ROXANA SCHILLACI

Chicago, IL

Congreso; 103rd Annual Meeting of the American Association for Cancer Research; 2012

AACR

Having in mind that Stat3 inhibition in tumor cells induces the expression of chemokines and pro-inflammatory cytokines, we proposed the use of Stat3-inhibited breast cancer cells as a source of immunogens to induce an anti-tumor immune response. We have demonstrated that the administration of irradiated breast cancer cells that express a dominant negative (DN) form of Stat3 (Stat3Y705F-breast cancer cells) provides protection against the murine progestin-dependent C4HD tumor, through the activation of CD4+ T cells and cytotoxic natural killer (NK) cells. To extend our results to different breast cancer model, we used the hormone independent 4T1 mammary carcinoma cell line that displays constitutive activation of Stat3. Immunization with irradiated Stat3Y705F-4T1 cells prevented wild-type 4T1 tumor development in 50% of the challenged mice (P