Early lung cancer coopts immune cell into helping tumours invade the lungs

17 Jun 2021
Early lung cancer coopts immune cell into helping tumours invade the lungs

Immune cells that normally repair tissues in the body can be fooled by tumours when cancer starts forming in the lungs and instead help the tumour become invasive, according to a surprising discovery reported by Mount Sinai scientists in Nature in June.

The researchers found that early-stage lung cancer tumours co-opt 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 allows a tumour to hurt the tissues the macrophage normally repairs. This process allows the tumour to hide from the immune system and proliferate into later, deadly stages of cancer.

Macrophages play a key role in shaping the tumour microenvironment, the ecosystem that surrounds tumours in the body. By investigating this microenvironment, researchers can find key players that drive tumour 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 tumours and surrounding lung tissue in 35 patients to see the role of macrophages in the development of the tumours.

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 tumour samples, samples of surrounding healthy lung tissue, and blood samples were immediately analysed 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 tumours 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 tumour progression in patients at risk by reprogramming macrophages and killing the tumour without surgery."

Source: The Mount Sinai Hospital / Mount Sinai School of Medicine