Combination of Cy and AdIL-12 enhances in vivo antitumor immune response by reversion of Tregs and MDSC-driven immunosuppression

MALVICINI, MARIANA; INGOLOTTI, MARIANA; PICCIONI, FLAVIA; GARCIA, MARIANA; BAYO, JUAN; ATORRASAGASTI, CATALINA; ALANIZ, LAURA; SCHAROVSKY, GRACIELA; MATAR, PABLO; MAZZOLINI, GUILLERMO

Ciudad de Buenos Aires

Congreso; First French-Argentine Immunology Congress; 2010

FAIC

We have previously demonstrated the synergistic antitumor effect of the sequential administration of low-dose cyclophosphamide (Cy) followed by sub-therapeutic doses of adenovirus expressing IL-12 genes (AdIL-12) in a mouse colorectal carcinoma (CRC) model (CT26). Our results suggested that the combined treatment allowed the generation of strong antitumor immune responses. The aim of this work was to investigate the immunological mechanisms responsible for the therapeutic effect of the combination. Methods: Balb/c mice were s.c injected with CT26 cells (day 0), distributed in experimental groups (day 7) and treated with: saline; Cy 50 mg/Kg i.p (day 7); AdIL-12 109 TCID50 i.t (day 8) or Cy + AdIL-12. Tumor volume was measured and samples of peripheral blood, spleen and tumor were taken. CD4+CD25+ and CD4+CD25- T lymphocytes were isolated by magnetic separation. Results: We observed that mice nonresponder to the combined treatment showed a proportion of regulatory T cells (Tregs) higher than in responder mice, both in peripheral blood and spleen, as well as in tumor samples (p