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A small group of cells lining blood vessels may play an unexpected role in helping the immune system find and attack metastatic cancer, according to new research that could eventually open new avenues for improving immunotherapy.
The study, which focused on cancers that have spread to the liver, found that these specialized blood vessel cells appear to act as guides for cancer-fighting T cells, helping them leave the bloodstream and enter tumors. Researchers say the discovery could help explain why some tumors are packed with immune cells while others remain largely untouched by the body’s defenses.
One of the biggest obstacles facing cancer immunotherapy is that, in many patients, too few T cells reach the tumor to mount an effective attack. To investigate why, researchers examined liver metastases, which are common in advanced cancer and are often resistant to immunotherapy.
They identified a distinct subset of endothelial cells—the cells that form the inner lining of blood vessels—that produce lipoprotein lipase (LPL), an enzyme primarily known for its role in fat metabolism. The researchers found that these cells do far more than support blood flow.
Instead, they appear to help T cells recognize where tumors are located by displaying tumor-derived material on their surface, allowing immune cells circulating in the blood to identify the cancer and move into the tumor tissue.
Tumors with larger numbers of these LPL-producing blood vessel cells also contained more T cells, the researchers found.
In mouse models of melanoma that had spread to the liver, increasing LPL levels in the endothelial cells led to greater T-cell infiltration and stronger tumor shrinkage. Removing LPL had the opposite effect, weakening the immune response.
Hellmut Augustin, director of the Department of Vascular Oncology and Metastasis at the German Cancer Research Center (DKFZ) and Heidelberg University, told Newsweek that the findings overturned one of the team’s central expectations.
Because tumors are known to suppress immune activity, the researchers anticipated that blood vessel cells inside tumors would also discourage T cells from entering. Instead, the first immune cells to arrive appeared to trigger changes in the endothelial cells that encouraged even more T cells to follow.
“Simplistically and metaphorically, one could say that the first arriving T cells elicit a program through which they call in their brothers and sisters,” Augustin said.
The observation hints at a broader question that the researchers are now exploring.
“It is tempting to speculate that this could be the tipping point that decides if a tumor is immunologically ‘hot’ or ‘cold,'” Augustin said. But he cautioned against drawing firm conclusions, adding, “Clearly, we would need more data to formally conclude that.”
The team was also surprised that the effect was driven by only a relatively small population of endothelial cells rather than by blood vessels throughout the tumor.
The researchers believe these specialized cells could become a future therapeutic target. In the current study, they genetically increased LPL production to demonstrate that boosting the pathway improved T-cell function and reduced tumor growth in mice. The next challenge will be finding drug-based approaches that produce the same effect.
According to Augustin, that work will include investigating compounds that mimic LPL or identifying ways to stimulate tumor blood vessels to make more of the enzyme naturally. The team also plans to study exactly how LPL enables these endothelial cells to take on their unexpected immune role.
Despite the promising findings, Augustin emphasized that the research remains at an early stage.
“This is all early days of mechanism-based preclinical discovery research,” he said. While the work “offers perspective,” he added, it “has no immediate consequences for tumor patients today.”
If confirmed in future studies, the findings could reshape scientists’ understanding of tumor blood vessels—not simply as structures that nourish cancer, but as active players that help determine whether the immune system can gain access to metastatic tumors in the first place.
Reference:
Xiaowen Zhang, Miki Kamiyama, Margaret Tulessin, Lorna Rinck, et al. LPL-positive endothelial cells control T cell homing in liver metastasis. Cancer Discovery 2026, DOI: https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-25-1411
Contact Newsweek editors on this story: Kara Dolman and Emma Lee-Sang
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