Tumor microenvironment, including endothelial cells and tumor associated macrophages (TAMs) but also hypoxia, favors tumor growth. Hypoxia initiates angiogenesis, recruitment of monocytes, which become TAMs, and favors cancer cell resistance to anti-cancer agents. If these effects are well described, few data are available regarding the reciprocal effects of TAMs on endothelial cells and on cancer cells. Even less known is the influence of hypoxia on these parameters. In this context, we developed unique cell models which were instrumental to demonstrate that TAMs induce tumor chemoresistance and that cycling hypoxia initiates a positive endothelial- dependent pro-inflammatory feed back. In this project we now aim to investigate whether cycling or chronic hypoxia modulates or drives the dialogue between the different cell types present in tumors and to study the consequences of these interactions on tumor growth and resistance. These studies will be performed in vitro, in mice models as well as in patients. Targets could be identified to design new treatments to be combined with targeted or classical chemotherapy.
|Effective start/end date||1/10/14 → 30/09/16|