Study: Vessels that Spread Cancer Can Also Boost Immunotherapy

A lymphatic vessel (green) inside a Braf-driven primary mouse melanoma tumor. (Manuel Fankhauser and Maria Broggi / EPFL)A lymphatic vessel (green) inside a Braf-driven primary mouse melanoma tumor. (Manuel Fankhauser and Maria Broggi / EPFL)

Researchers have discovered that lymphatic vessels, which are often blamed for enabling cancer to spread, can also boost immunotherapy, a type of cancer treatment that activates the body’s own immune system to fight the disease. 

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The thin tubes carry white blood cells and lymph through the lymphatic system, which helps protect the body from infection, according to the National Institutes of Health.

Lymphatic vessels can expand around and into a tumor – a process known as lymphangiogenesis that’s associated with a cancer’s ability to spread to new areas and evade a patient’s own immune system.

A new study found that the same process can strongly enhance the effects of immunotherapy in melanoma patients being treated with checkpoint inhibitors – drugs that help activate an immune response against tumors by boosting the ability of cancer-fighting T cells to infiltrate tumors and kill cancer cells.

“Our study presents a completely unexpected role for the lymphatic system in cancer therapy,” said University of Chicago researcher Melody Swartz, in a statement.

Though promising, immunotherapies are only effective in a minority of patients, according to researchers.

One of the problems is that many tumors evolve to evade or survive attacks by a patient’s immune system. For example, melanomas induce lymphangiogenesis with a protein called Vascular Endothelial Growth Factor C (VEGF-C), which has been associated with metastasis and poor patient prognosis, according to researchers. Recent studies have also suggested the protein may aid melanoma tumors in suppressing a patient’s immune system.

Since VEGF-C was always considered “bad” for cancers, researchers initially thought blocking the protein would boost immunotherapy by removing some factors that suppress the abilities of T cells to kill tumor cells, said Swartz.

To researchers’ surprise, their studies in mouse models and two clinical trials in melanoma patients revealed the opposite. Scientists found blocking VEGF-C had a negative impact on immunotherapy. “The difference was striking,” Swartz said.

Before each trial, researchers took blood samples and found “almost all of the patients with higher-than-average VEGF-C levels in their blood responded to immunotherapy,” Swartz said. “This not only resulted in eradication of primary tumors, it also encouraged T cell infiltration into metastatic tumors and resulted in long-term protection.”

Researchers posit that VEGF-C could become a useful biomarker because it’s easy to measure from a blood sample. “It can predict who is likely to respond. If VEGF-C is low, immunotherapy is much less likely to be effective,” Swartz said.

Researchers acknowledge there are several limitations, including the potential effects of VEGF-C on other immune cell subsets, the contributions of other cytokines and competition with other T cells for nutrients. Despite that, the study “brings into focus a more comprehensive understanding of the immune microenvironment,” said Swartz.

The study was funded by the Swiss National Science Foundation, the European Research Council, SwissTransMed and Fonds Pierre-François Vitttone.

Follow Kristen Thometz on Twitter: @kristenthometz

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