Reversal of gastrointestinal carcinoma-induced immunosuppression and induction of antitumoural immunity by a combination of cyclophosphamide and gene transfer of IL-12
- Malvicini, Mariana
- Ingolotti, Mariana
- Piccioni, Flavia Valeria
- García, Mariana Gabriela
- Bayo Fina, Juan Miguel
- Atorrasagasti, María Catalina
- Alaniz, Laura Daniela
- Aquino, Jorge Benjamin
- Espinoza, Jaime A.
- Gidekel, Manuel
- Scharovsky, Olga Graciela
- Matar, Pablo
- Mazzolini Rizzo, Guillermo Daniel
DOIAbstract
Immunotherapy-based strategies for gastrointestinal carcinomas (GIC) have been exploited so far, but these approaches have to face strong mechanisms of immune escape induced by tumours. We previously demonstrated that sub-therapeutic doses of an adenovirus expressing IL-12 genes (AdIL-12) mediated a potent antitumour effect against subcutaneous (s.c.) colorectal carcinomas (CRC) in mice pre-treated with low doses of cyclophosphamide (Cy). In our study we used this combination to assess its impact on the immunosuppressive microenvironment. In s.c. CRC model we demonstrated that non-responder mice failed to decrease Tregs in tumour, spleen and peripheral blood. Reconstitution of Tregs into tumour-bearing mice treated with combined therapy abo...
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