Cancer’s Immune Evasion Blocked by Blocking LCN2 Protein, Study Finds

By Dr. Priya Deshmukh – Senior Editor, Health

February 18, 2026

New research from NYU Langone Health sheds light on how cancer cells evade the body’s natural defenses, offering a potential new avenue for treatment. Scientists have discovered that a protein released by stressed cancer cells, lipocalin 2 (LCN2), acts as a shield, preventing the immune system from recognizing and attacking tumors – particularly in lung and pancreatic cancers. This finding suggests that blocking LCN2 could make aggressive cancers more susceptible to existing immunotherapies.

How Cancer Cells Evade the Immune System

The immune system is often the body’s most powerful weapon against cancer. Immunotherapy works by boosting this natural ability, but many tumors develop ways to circumvent immune responses. Understanding these evasion tactics is crucial for developing more effective cancer treatments. The research team’s work focuses on the complex interplay between cancer cells and the immune microenvironment, aiming to dismantle the mechanisms that allow tumors to remain hidden.

The Role of LCN2 in Shielding Tumors

Lipocalin 2, or LCN2, is a protein known to be elevated in various cancers and is often associated with inflammation and stress responses within tumor cells. Researchers found that when cancer cells are stressed, they release increased amounts of LCN2. This protein then interferes with the ability of immune cells, specifically T cells, to infiltrate the tumor and launch an attack.

By blocking the action of LCN2 in laboratory models, the researchers were able to restore the immune system’s ability to target and destroy cancer cells. This process effectively “unmasks” the tumors, making them visible to the immune system. As reported by Medical Xpress, the study involved a cellular survival pathway called the integrated stress response (ISR), which cells use to endure stressful conditions.

LCN2 and the Integrated Stress Response

Cancer cells, with their abnormal, aggressive growth, face a continual threat of starvation and are always stressed, constantly having the ISR turned on. The ISR in cancer cells triggers the production of a protein called Activating Transcription Factor 4 (ATF4), which then triggers the action of many genes that help cancer cells survive. The new work shows that ATF4 also instructs the cell to release LCN2 to protect the tumor from the immune system.

“Stressed cancer cells have learned to call for help through LCN2, which shields them from the immune system,” said co-corresponding study author Thales Papagiannakopoulos, PhD, associate professor in the Department of Pathology at the NYU Grossman School of Medicine. Life Technology Medical News details how LCN2 passes on the ATF4 message to switch macrophages, a type of immune cell abundant in tumors, into an “immunosuppressive” mode, keeping cancer-killing T cells from entering the tumor.

Research Findings and Patient Outcomes

Researchers engineered mice to both develop cancer and lack LCN2, resulting in slowed tumor growth. This effect occurred only in mice with healthy immune systems, suggesting that LCN2’s primary role is to block the immune attack on tumors.

An examination of tumor samples from over 100 lung cancer patients and 30 pancreatic cancer patients revealed a correlation between high LCN2 levels and reduced survival rates. Patients with high LCN2 levels had a median survival of 52 months, compared to 79 months for patients with low levels.

When treated with an antibody that blocked LCN2, tumors in mice were flooded with T cells and shrank. Combining the LCN2 antibody with an existing immunotherapy drug further extended survival in mice with aggressive lung cancer.

“Our results provide a clear rationale for developing therapies that target LCN2 in lung cancer patients,” said co-corresponding study author Shohei Koide, PhD, professor in the Department of Biochemistry and Molecular Pharmacology at NYU Grossman School of Medicine, and director of Cancer Biologics at Perlmutter Cancer Center. “We also aim for to explore whether this mechanism is active in other cancer types that resist immunotherapy.”

NYU Langone Health and Cancer Treatment

NYU Langone Health’s Perlmutter Cancer Center specializes in treating non-slight cell and small cell lung cancer, as well as mesothelioma. NYU Langone Health offers a comprehensive range of medical services and is consistently ranked among the top hospitals in the nation for patient outcomes.