DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

NRF2 Pathway Activation in the Lung Tumor Microenvironment Macrophages

Principal Investigator: MENDES LEAL, ANA SOFIA
Institution Receiving Award: MICHIGAN STATE UNIVERSITY
Program: LCRP
Proposal Number: LC210240
Award Number: W81XWH-22-1-0027
Funding Mechanism: Career Development Award
Partnering Awards:
Award Amount: $391,250.00


PUBLIC ABSTRACT

The lung is rich in macrophages, specialized immune cells that remove toxic/harmful particles generated either by normal functions of the lung (breathing) or by exposure to external factors such as bacteria or pollutants. Lung cancer cells can hijack macrophages to support their growth and suppress the action of cancer eliminating T cells (another component of the immune system). One of the functions of macrophages that can be repurposed by cancer cells is the detoxifying system. The proposed work will investigate how cancer cells hijack the macrophages and the detoxifying system to promote tumor growth and exclude T cells.

The proposed work will help us understand how the interaction of cancer cells with immune cells can drive tumor growth. Furthermore, the mechanistic insights can unveil new therapeutic opportunities, both for prevention and treatment of lung cancer.

My main goal is to understand how cancer cells interact with the surrounding environment, particularly with immune cells, and how this interaction creates a supportive system for tumor cells to thrive, and therefore become a recognized academic expert in lung cancer tumor microenvironment interactions.

This funding opportunity will further reinforce my commitment to lung cancer research. Furthermore, the data generated will allow me to publish in the area of lung cancer and apply for other funding opportunities. Additionally, the planned participation in dedicated lung cancer meetings will enhance my opportunities to collaborate and share my scientific discoveries to help advance lung cancer treatment.

The novelty of the proposed work in lung cancer will result in at least one peer reviewed publication. Moreover, the planned attendance at national/international lung cancer meetings will allow me to interact with and establish collaborations within the lung cancer field.

Lung cancer is the most often diagnosed cancer in Service Members and in the overall population, and despite recent advances in therapeutic approaches, still has the highest mortality rate among all diagnosed cancers. Due to lifestyle and exposure during Service, military Service Members are more likely to have overactivated macrophages in their lungs engaged in detoxifying processes. Understanding the biological interactions of macrophages and cancer cells can reveal new therapeutic opportunities and improve current treatments by optimizing administration regimens.