Abstract
Despite significant advances, cancer immunotherapies fail to systematically elicit tumor regression. It is therefore crucial to understand what conditions the efficacy of immune responses against solid tumors. In particular, while the involvement of T lymphocytes does not need to be further proven, their relative contribution and their cooperation with other cells in regressing tumors is still ill defined. We have investigated in a breast tumor model (PyMT-MMTV) the dynamics of the immune response which takes place during the tumor regression induced by a single i.p. injection of DMXAA, a ligand and activator of STING (a key detector of cytoplasmic DNA and of viral infection). We have shown that the DMXAA-induced tumor vascular disruption, visualized by contrast-enhanced ultrasound, and the associated IFNα/β release, conditioned a swift and massive recruitment of neutrophils, followed by a delayed rise in CD8 T cells and inflammatory monocytes in the tumor mass. All these immune cell subsets contributed to the efficacy of tumor regression, as evidenced by in vivo depletion experiments, which, together with dynamic imaging allowed to characterize cooperations between these immune cell subsets. We have analyzed the kinetics of the biphasic effect of DMXAA : vascular disruption followed by an anti-tumoral immune response. These data support the idea that the inflammation in the tumor microenvironment can be modulated to reset immune cell cooperation like in an acute phase of an immune response against foreign pathogens.
Note: This abstract was not presented at the conference.
Citation Format: Julia M. Weiss, Marion Guerin, Fabienne Regnier, Maxime Thoreau, Elisa Peranzoni, Vincent Feuillet, Gilles Renault, Thomas Guilbert, Alain Trautmann, Nadege Bercovici. Biphasic anti-tumoral effect of a vascular-disrupting agent triggering STING and tumor regression. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr A05.
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