Published on Feb. 21, 2026
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Researchers at NYU Langone Health have discovered that a protein called lipocalin 2 (LCN2) plays a key role in helping cancer cells evade the immune system, particularly in lung and pancreatic cancers. The study, published in Nature, reveals that stressed cancer cells release LCN2, which manipulates surrounding immune cells and prevents them from attacking the tumor.
Why it matters
This breakthrough offers promising new avenues for enhancing cancer treatments, especially immunotherapies. By blocking LCN2, researchers were able to restore the function of immune cells and allow them to infiltrate and destroy cancer cells in mouse models. Targeting LCN2 could help overcome cancer’s ability to shield itself from the body’s natural defenses.
The details
The integrated stress response (ISR) in cancer cells triggers the production of Activating Transcription Factor 4 (ATF4), which instructs the cell to release LCN2. LCN2 then switches macrophages, a type of immune cell, into an ‘immunosuppressive’ mode, preventing cancer-killing T cells from reaching the tumor. Blocking LCN2 restored the function of these macrophages and allowed T cells to attack the cancer.
The study was published in Nature on February 18, 2026.Researchers engineered mice to lack LCN2 and observed slowed tumor growth.
The players
NYU Langone Health
A leading academic medical center in New York City where the research on LCN2 was conducted.
Lipocalin 2 (LCN2)
A protein released by stressed cancer cells that helps tumors evade the immune system.
Activating Transcription Factor 4 (ATF4)
A cellular protein that instructs cancer cells to release LCN2 in response to stress.
Macrophages
A type of immune cell found abundantly within tumors that LCN2 manipulates to suppress the immune response.
T cells
Cancer-killing immune cells that are prevented from infiltrating the tumor by LCN2.
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What’s next
Researchers are keen to investigate whether LCN2 plays a similar role in other cancer types that are resistant to immunotherapy, and to explore combining LCN2-targeted therapies with other immunotherapy approaches.
The takeaway
The discovery of LCN2’s role in helping tumors evade the immune system could lead to the development of new personalized immunotherapy regimens and LCN2-targeted drugs, potentially improving outcomes for patients with lung, pancreatic, and other hard-to-treat cancers.
