Lung Cancer & Immune System: Fueling Growth
- Lung adenocarcinoma, the leading cause of cancer-related deaths in the United States, often arises from mutations in the epidermal growth factor receptor (EGFR) protein.
- Researchers at the Salk Institute investigated this treatment gap and discovered that EGFR-driven lung adenocarcinoma cells hijack macrophages, a type of lung-resident immune cell.
- 25, 2024, suggests new approaches to disrupt the relationship between tumor cells and macrophages.
Discover how lung cancer, specifically lung adenocarcinoma, fuels its growth by exploiting the body’s own immune system. Researchers unveiled that tumor cells hijack macrophages, crucial lung-resident immune cells, changing their lipid metabolism to accelerate tumor progression. This groundbreaking process highlights why current immunotherapies struggle. The study suggests that combining EGFR inhibitors with statins could offer a new treatment strategy. News Directory 3 explores the critical role of macrophages in this process and the potential for new therapies. Uncover how researchers are disrupting this hazardous cycle. Discover what’s next in the fight against lung cancer.
Lung Cancer Cells Exploit Immune Cells for Fuel, Study Finds
Lung adenocarcinoma, the leading cause of cancer-related deaths in the United States, often arises from mutations in the epidermal growth factor receptor (EGFR) protein. While normal EGFR helps cells recover from injury, mutated EGFR can trigger uncontrolled growth, leading to cancer. Current immunotherapies are ineffective against EGFR-driven lung adenocarcinoma, and existing drug treatments often lose their effectiveness as patients develop resistance.
Researchers at the Salk Institute investigated this treatment gap and discovered that EGFR-driven lung adenocarcinoma cells hijack macrophages, a type of lung-resident immune cell. Macrophages typically remove diseased cells and maintain a balance of lipids around lung alveoli, which are essential for breathing. However, cancer cells manipulate macrophages within the tumor microenvironment, altering their lipid metabolism to provide fuel for tumor growth. This process creates a self-perpetuating cycle where tumor cells stimulate macrophage proliferation to increase fuel supply, driving cancer progression.
The study, published in *Cancer Discovery* on Jan. 25, 2024, suggests new approaches to disrupt the relationship between tumor cells and macrophages. The researchers propose that combining EGFR inhibitors with statins,commonly used to lower cholesterol,may improve treatment outcomes for lung adenocarcinoma.
“We have discovered a novel way that lung cancer cells manipulate their local habitat and other cell types surrounding them to promote their own growth,” said Susan Kaech, professor and director of the NOMIS Center for Immunobiology and Microbial Pathogenesis at salk. “One exciting implication of this work is that lung cancer treatments may be improved by simply adding statins, an already widely used class of drugs, to the patient’s treatment plan.”
Alexandra Kuhlmann-Hogan, former postdoctoral researcher in Kaech’s lab and current postdoctoral researcher at UC Los Angeles, noted that tumor cells secrete granulocyte macrophage colony-stimulating factor (GM-CSF), causing macrophages to grow and change their metabolism. This results in excess lipids that the tumor cells use to strengthen themselves. “The cancer was effectively hijacking this normal macrophage process of maintaining the lungs with healthy lipids in order to fuel itself,” Kuhlmann-Hogan said.
Katerina Politi,scientific director of the center for thoracic Cancers at Yale Cancer Center,added that the tumor cells not only reprogram the macrophages metabolically but also instigate a feedback loop that encourages an optimal metabolic state in the tumor cells themselves.
The researchers found that GM-CSF secreted by EGFR-driven lung adenocarcinoma cells stimulates a gene in macrophages called PPARγ, which initiates metabolic reprogramming and lipid secretion. The tumor cells use these lipids to grow and to power the continued activation of the EGFR-drive that helps the cancer grow.
Christian Metallo, professor at Salk, said the results reveal new therapeutic possibilities for immunotherapy-resistant EGFR-driven lung adenocarcinomas. “we have identified a key metabolic relationship between macrophages and alveoli that is exploited by tumor cells to support the cancer’s metabolic demands — now we just have to disrupt that exploitation,” Metallo said.
What’s next
The researchers suggest that future clinical trials should explore combining PPARy inhibitors,to disrupt macrophage hijacking,with statins,to limit available cholesterol,alongside existing EGFR inhibitors. They also plan to investigate whether similar immunological hijacking occurs in other tumor microenvironments.