ECONOMY · Endothelial Cells - an Overlooked Non-hematopoietic cOmponent of tuMor immunitY

Endothelial Cells - an Overlooked Non-hematopoietic cOmponent of tuMor immunitY

In this study, we analyzed the interactions of endothelial cells with immune cells in the context of lung cancer. Immune cells are the body’s natural defense against harmful substances and microorganisms, as well as abnormal tumor cells arising in the body. However, their ability to fight tumor cells is often hampered by interactions with other cell types and factors secreted to the environment around the tumor that can render these immune cells inert. Many cancer therapies are designed to re-activate the immune cells, and thereby activate the body’s own defense mechanism against the tumor (so-called immunotherapies). Although such treatments have proven successful in some cancer patients, these therapies often encounter resistance in the majority of cases. Furthermore, in cases of intital treatment success, patients often relapse later on. To improve these therapies, it is necessary to gain a better understanding of how immune cells are impacted by the cells surrounding them. Endothelial cells are the cells that line the inner walls of blood vessels, and therefore function as a barrier between the tumor and the blood stream, where the immune cells are recruited from. Thus, immune cells have to pass through the endothelial cell layer to reach the tumor. Potential interactions between endothelial cells and immune cells could therefore be very significant, as they may change the characteristics of immune cells before they encounter the tumor cells. Very interestingly, it has been observed that endothelial cells express proteins that are known to modulate the immune system (so-called immunoregulatory proteins). This was surprising, because such molecules are usually only found on different types of immune cells, or on cancer cells. However, it remains unknown if endothelial cells could interact with immune cells via these proteins. In our study, we investigated the role of endothelial cells expressing immunoregulatory proteins in tumors. We studied their interactions with immune cells, and examined how those impacted tumor growth and the response to immunotherapy. Using animal models of lung cancer, we identified a potential biomarker that may predict the response of the tumor to immunotherapy (see below). Currently our results are validated in clinical samples. Our results will ultimately (a) help to better identify the patients most likely to respond to immunotherapy, and (b) lead to future work involving modulating the tumor immunity by altering the endothelial barrier to enhance the efficacy of immunotherapies.

Data: CORDIS, © European Union