Early Lung Cancer Coopts Immune Cell Into Helping Tumors Invade the Lungs, Mount Sinai Researchers Discover
Immune cells that normally repair tissues in the body can be fooled by tumors when cancer starts forming in the lungs and instead help the tumor become invasive, according to a surprising discovery reported by Mount Sinai scientists in Nature in June.
The researchers found that early-stage lung cancer tumors coopt the immune cells, known as tissue-resident macrophages, to help invade lung tissue. They also mapped out the process, or program, of how the macrophages allow a tumor to hurt the tissues the macrophage normally repairs. This process allows the tumor to hide from the immune system and proliferate into later, deadly stages of cancer.
Macrophages play a key role in shaping the tumor microenvironment, the ecosystem that surrounds tumors in the body. By investigating this microenvironment, researchers can find key players that drive tumor growth that can be tested as targets for immunotherapy. But modifying macrophages therapeutically has proven difficult.
In this study, scientists studied tissue samples from lung cancer tumors and surrounding lung tissue in 35 patients to see the role of macrophages in the development of the tumors.
The study’s lead author, Miriam Merad, MD, PhD, Director of the Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai, and a multidisciplinary team of thoracic surgeons, pathologists, and medical oncologists within the Institute of Thoracic Oncology devised a comprehensive study that began when patients went into surgery to have cancerous lesions removed. The patients’ lung tumor samples, samples of surrounding healthy lung tissue, and blood samples were immediately analyzed on a cellular level at Mount Sinai’s Human Immune Monitoring Center to map out the immune system components they contained.
Researchers identified the macrophages at play in the early development of lung cancer, identifying a potential target for future drug development. They also found that the process that allows the macrophages to help tumors invade lung tissues is present in mice as well, which will allow them to manipulate the macrophages in future mouse models knowing that the manipulation is relevant to humans.
Half of all early-stage lung cancers relapse, and once they do and reach later stages, it is deadly and irreversible. Knowing how to attack the cancer at an early stage could have huge impacts on the number of patients relapsing and their overall survival.
“These findings are very important for Mount Sinai in the future as we have a very strong lung cancer screening program that identifies patients with early lung cancer lesions before they become fully invasive,” said Dr. Merad, who is also the Director of the Human Immune Monitoring Center and a member of the Institute of Thoracic Oncology and The Tisch Cancer Institute at Mount Sinai. “These findings will help devise immunoprevention strategies to prevent tumor progression in patients at risk by reprogramming macrophages and killing the tumor without surgery.”
About the Mount Sinai Health System
Mount Sinai Health System is one of the nation’s leading integrated academic health systems and one of the largest in the New York metropolitan area. Its comprehensive system includes seven hospitals, more than 400 outpatient practices, over 600 research and clinical laboratories, the Icahn School of Medicine at Mount Sinai, the Graduate School of Biomedical Sciences, and the Mount Sinai Phillips School of Nursing. Together, the Health System comprises approximately 48,000 employees, more than 9,000 physicians, and 8,600 nurses.
As a leading learning health system, Mount Sinai combines clinical expertise with scientific discovery to improve patient care while training the next generation of health care and biomedical leaders. The Health System provides care across every stage of life, from prenatal care through geriatrics, while advancing personalized medicine through artificial intelligence, data science, and biomedical research.
Mount Sinai is consistently recognized among the nation’s leading academic health systems for patient care, research, and education. The Mount Sinai Hospital is ranked No. 1 in New York by Newsweek and No. 5 on the magazine’s World’s Best Hospitals list. The Icahn School of Medicine at Mount Sinai ranks No. 11 among U.S. medical schools and No. 1 among freestanding medical schools for National Institutes of Health funding, reflecting the strength of its scientific enterprise and leadership in biomedical research.
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