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- Local IFNα enhances the anti-tumoral efficacy of systemic anti-PD1 to prevent tumor relapse
Local IFNα enhances the anti-tumoral efficacy of systemic anti-PD1 to prevent tumor relapse
Authors
Marion v Guerin, Fabienne Regnier, Maxime Thoreau, Lene Vimeux, Matthieu Benard, Estelle Dransart, Hweixian L Penny, Ludger Johannes, Alain Trautmann, Nadege Bercovici
Abstract
Background
Tumor relapse constitutes a major challenge for anti-tumoral treatments, including immunotherapies. Indeed, most cancer-related deaths occur during the tumor relapse phase.
Methods
We designed a mouse model of tumor relapse in which mice transplanted with E7
Results
We show that, during the regression phase, tumors of mice treated with a single vaccination of STxB-E7 + IFNα harbor fewer activated CD8 T cells and monocytes than tumors doomed to fully regress after two vaccinations. In contrast, the systemic injection of an anti-PD1 Ab combined with the peri-tumoral injection of IFNα in this time frame promotes infiltration of activated CD8 T cells and myeloid cells, which, together, exert a high cytotoxicity in vitro against TC1 cells. Moreover, the IFNα and anti-PD1 Ab combination was found to be more efficient than IFNα or anti-PD1 used alone in preventing tumor relapse and was better able to prolong mice survival.
Conclusions
Together, these results indicate that the local increase of IFNα in combination with an anti-PD1 therapy is an effective way to promote efficient and durable innate and adaptive immune responses preventing tumor relapse.
Members
LUDGER JOHANNES
Directeur de recherche Inserm