New immune-targeted therapeutic may reduce lung cancer tumors

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A preclinical study has identified the possibility of an innovative therapeutic strategy for treating patients with non-small cell lung cancer (NSCLC), which makes up almost 85% of all lung cancers. Researchers at the Icahn School of Medicine at Mount Sinai in New York City demonstrated the approach. It involves impeding TREM2, the immune-system molecule, while developing natural killer cells, a type of white blood cells that protects the immune system. Outcomes and details of the study were published in Nature Immunology’s April 20 online issue.

“Our study reveals that macrophages expressing the molecule TREM2 drive the depletion and dysfunction of effector immune cells called natural killer cells, known to play a key role in the elimination of cancer cells, providing a strong rationale for the clinical development of combination therapies that concurrently block TREM2 and boost natural killer cells,” said Matthew Park, an MD/PhD candidate and first author of the study.

According to prior research, majority of the tumors found in patients who have NSCLC and other types of cancer lack enough or any natural killer (NK) cells, whose primary function is to detect and destroy malignant cancer cells. Although researchers don’t yet know why these tumors are initially deprived of NK cells, they have recently begun to understand how tumors avoid the NK cells when they do exist.

This study revealed the cause to be another type of immune cell called macrophages. Researchers discovered that as tumors progress, macrophages located in the bone marrow suppress the occurrence and stimulation of NK cells. 

The team’s sequencing tests, performed on mice, sought to determine which genes were producing this act. Results indicated that lung tumor growth significantly decreased when restricting TREM2 activity or preventing it from binding with an antibody.

“We identified a novel axis of immunity, whereby TREM2-expressing macrophages regulate the recruitment and activity of natural killer cells during lung tumor progression, and showed preclinical evidence for a new therapeutic strategy that combines TREM2 blockade and natural killer cell activation using an antibody developed by [Lucas Ferrari de Andrade, PhD],” said Miriam Merad, MD, PhD.

Dr. Merad, senior author of the paper, is director of the Precision Immunology Institute and director of the Human Immune Monitoring Center at Icahn Mount Sinai. Co-author Dr. Ferrari de Andrade is an assistant professor of Oncological Sciences at Icahn Mount Sinai and a member of the Precision Immunology Institute and the Tisch Cancer Center.

Other current studies suggest that interference of TREM2 cells is not globally therapeutic, but the Icahn Mount Sinai research team plans to clarify this application among other cancers.

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