February 25, 2024
Understanding How Lung Cancer Exploits Immune Cell Metabolism to Promote Growth

Understanding How Lung Cancer Exploits Immune Cell Metabolism to Promote Growth

Lung adenocarcinoma, the most common type of lung cancer in the United States, is also the leading cause of cancer-related deaths. One of the ways this cancer can develop is through a mutation in a protein called EGFR (epidermal growth factor receptor). While non-mutated EGFR promotes controlled cell growth in response to injury, mutated EGFR leads to uncontrolled growth, which can lead to cancer. Unfortunately, current immunotherapies are ineffective against EGFR-driven lung adenocarcinoma, and existing drugs often face resistance within a short period of time. To address this treatment gap, researchers from the Salk Institute sought to identify vulnerabilities in the cancer’s growth pathway.

The team discovered that EGFR-driven lung adenocarcinoma manipulates a specific group of immune cells called macrophages, which reside in the lungs and are responsible for eliminating damaged or diseased cells. Macrophages also help maintain the necessary balance of protective lipids in lung alveoli, which are vital for proper breathing.

The cancer cells coax macrophages into the tumor microenvironment and alter their metabolism to become a fuel source for cancer growth. This newly energized tumor cells then stimulate increased macrophage production, resulting in a self-perpetuating mechanism for cancer progression.

Published in Cancer Discovery, this groundbreaking research offers new insights for interventions targeting lung adenocarcinoma by disrupting the interaction between tumor cells and macrophages. The researchers suggest that combining EGFR inhibitors with statins, a class of drugs that lower cholesterol levels, could improve treatment outcomes.

“Our findings reveal a novel way in which lung cancer cells exploit their surroundings and manipulate nearby cell types to fuel their own growth. In this case, the tumor cells reprogram lung-resident macrophages, using them to provide nutrients such as cholesterol to support cancer growth,” explains senior author Susan Kaech, a professor and director of the NOMIS Center for Immunobiology and Microbial Pathogenesis at the Salk Institute. “One exciting implication of this work is that lung cancer treatments could potentially be enhanced simply by adding statins, which are already widely used, to the patient’s treatment plan.”

The health of the lungs relies on tiny structures called alveoli, which expand and contract with each breath, facilitating the exchange of oxygen and carbon dioxide in the bloodstream. Alveoli play a critical role in human survival, and their well-being depends on a lipid-rich environment maintained by alveolar cells and macrophages. Lipids, including cholesterol, are essential fatty compounds that support various bodily functions, such as cell movement, energy storage, and vitamin absorption.

However, the ability of lung-resident macrophages to regulate lipid balance becomes more complex when tumor cells exploit these lipids for their growth. By uncovering the mechanisms macrophages employ to regulate metabolism and lipid production, researchers can gain insights into how tumor cells manipulate these processes for their benefit. This understanding opens up new possibilities for developing targeted therapies that disrupt the interaction between tumor cells and macrophages, offering hope for improved outcomes in lung adenocarcinoma treatment.