Le cancer du poumon et la séduction de notre système immunitaire inné: Le role des neutrophiles lors de la progression du cancer du poumon

 

Jonathan Spicer

Institut de recherche du Centre universitaire de santé McGill

 

Domaine :  cancer

Programme chercheurs-boursiers-cliniciens - Junior 1

Concours 2017-2018

This study is designed to expand our understanding of how our immune system interacts with a growing lung cancer. Neutrophils are known to be important players in the tumor microenvironment. Indeed, patients with high levels of neutrophil infiltration seem to have worse outcomes. However, the mechanisms by which neutrophils are recruited into a growing cancer and their exact functional role within these cancers are poorly understood phenomena. In addition, we and others have found that inflammatory signals can trigger circulating neutrophils to release their intracellular DNA in a web-like fashion called Neutrophil Extracellular Traps or NETs. We have shown that these NETs are capable of facilitating cancer progression by trapping and promoting the growth of circulating tumor cells. We wish to establish how developing lung tumors do this and how it impacts patients in the clinical setting.

Therefore, our study draws from critically important source human tissues to establish the relevant candidate molecules that are associated with these phenomena, as well as cutting edge basic laboratory science to validate our findings. Once we have delineated the hierarchy of molecular signals that choreograph the ingress of neutrophils to developing cancers, we will study how the expression of these molecules within a large scale array of human lung cancers translates to patient survival and disease progression. Similarly, we will address how NET levels in human patient bloods can predict oncologic outcomes. The immediate impact of the proposed research is to provide the necessary fundamental understanding of how neutrophils influence lung cancer progression and behave functionally within the tumor microenvironment. The long-term impact of the findings from this study will form the basis for the development of novel therapeutic strategies to identify patients who are unlikely to benefit from conventional treatments and who may benefit from neutrophil directed therapeutics.