Antibody Targeting Stress Protein Boosts Cancer Immunotherapy in Mice

NYU researchers find blocking lipocalin 2 makes aggressive lung and pancreatic tumors more vulnerable to immune attack.

Published on Feb. 23, 2026

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A preclinical study led by researchers at NYU Langone Health found that a protein called lipocalin 2 (LCN2), produced by stressed cancer cells, helps lung and pancreatic tumors evade the immune system. The team developed an antibody therapy to block LCN2, which allowed the immune system to target and shrink tumors in mice. Combining the LCN2 antibody with existing immunotherapy drugs further extended survival in mice with aggressive lung cancer.

Why it matters

This research provides a potential new approach to improving cancer immunotherapies, which have shown limited effectiveness against certain aggressive tumor types. By targeting the LCN2 protein that cancer cells use to shield themselves from immune attack, the findings suggest a way to make these hard-to-treat cancers more vulnerable to immune-based treatments.

The details

The study, published in Nature, centered on the integrated stress response (ISR) pathway that cancer cells use to survive under stressful conditions like nutrient deprivation. The ISR triggers production of the ATF4 protein, which in turn instructs cancer cells to release LCN2. The researchers found that LCN2 then manipulates immune cells called macrophages, causing them to suppress the cancer-killing activity of T cells. When the researchers blocked LCN2 using an antibody, it allowed T cells to infiltrate and shrink tumors in mice.

  • The study was led by researchers at NYU Langone Health and published in the journal Nature on February 19, 2026.

The players

Thales Papagiannakopoulos

Associate professor in the department of pathology at the NYU Grossman School of Medicine and co-corresponding author of the study.

Shohei Koide

Professor in the department of biochemistry and molecular pharmacology at NYU Grossman School of Medicine, and director of cancer biologics at the Perlmutter Cancer Center, as well as co-corresponding author of the study.

Lipocalin 2 (LCN2)

A protein produced by stressed cancer cells that helps shield tumors from the immune system.

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What they’re saying

“Stressed cancer cells have learned to call for help through LCN2, which shields them from the immune system.”

— Thales Papagiannakopoulos, Associate professor (Nature)

“Our results provide a clear rationale for developing therapies that target LCN2 in lung cancer patients. We also want to explore whether this mechanism is active in other cancer types that resist immunotherapy.”

— Shohei Koide, Professor (Nature)

What’s next

The research team plans to further investigate whether the LCN2 mechanism is involved in other cancer types that are resistant to immunotherapy, and to continue developing antibody therapies targeting LCN2 for potential clinical use.

The takeaway

This study highlights a novel approach to improving cancer immunotherapies by targeting a stress protein that helps tumors evade the immune system. By blocking LCN2, researchers were able to make aggressive lung and pancreatic cancers in mice more vulnerable to immune attack, suggesting new possibilities for treating hard-to-treat cancers.