Exploring Granulopoiesis Alteration linked with the Chronic Inflammation contexture in Lung cancer – EGACIL

Neutrophils are known as the first barrier to bacterial challenge in acute inflammation, however characterizing their involvement in chronic inflammation and related diseases is an emerging research field. As they are characterized by an extremely short lifetime, homeostatic neutrophil biogenesis leads to the production of about hundrer million cells per day in human and the plasticity of this process appears complex and coordinated with neutrophil functional diversity, as illustrated in lung cancer and heart infraction model.

I am hypothesizing that accessing hematopoiesis plasticity in lung cancer patients and mouse models will allow to better understand its consequences on neutrophil origin, diversity and functions in an inflamed milieu.

• Primary objective: Characterization of the link between blood neutrophil alterations and diversity and its association with lung tumor infiltrating neutrophil function.
• Secondary objectives: Understanding how lung cancer development remotely alters the neutrophil biogenesis for the identification of novel therapeutic targets to reprogram the neutropoiesis.

The novelty of this project stems from the original observation that neutropoiesis alteration displays diverse pictures in NSCLC patients and mouse models which are linked with the response to imune chekpoint inhibitors. It aims at exploring the concept that specific tumor microenvironment architecture and neutrophil functional plasticity are not only driven from signals present into the tumor mass but also through a remote alteration induced by the lung tumor on the granulopoiesis itself.

The project will question the importance of innate immune cells pre-programing illustrating for the first time the concept of trained innate immunity in lung cancer patients toward the identification of novel predictive markers and the exploration of innovative therapeutic targets in pre-clinical mouse models.