Lymphatic vessels are tiny valved structures that transport and drain fluid from the body—but they are also blamed for carrying cancer cells from the primary tumor to other locations in the body. Now a research team led by the University of Chicago has discovered that these vessels can turn from bad actors into treatment boosters by enabling immune cells to break into tumors and kill cancer cells.
Lymphatic vessels have the ability to wrap around tumors and weave through them, thereby allowing cancer cells to leave the primary site and spread throughout the body. But in patients being treated with immune checkpoint inhibitors like Bristol-Myers Squibb’s Yervoy and Opdivo, those same vessels enhance the power of cancer-killing T cells, the researchers discovered. Their findings were published in the journal Science Translational Medicine.
They key to the discovery, the researchers say, was a surprising revelation about a chemical messenger called vascular endothelial growth factor-C (VEGF-C). This chemical is associated with cancer metastasis, so it stands to reason that blocking it would help prevent the disease from spreading. Instead, the scientists discovered that high levels of VEGF-C in the blood correlated with positive responses to checkpoint blockade.
Checkpoint inhibitors have transformed the treatment of some cancers, most notably melanoma. But only 20% of patients are cured by the drugs, and many patients who do respond eventually become resistant to them. Several methods for solving this problem are under investigation, including combining the drugs with cancer-killing viruses and using a drug that improves blood flow to boost the population of beneficial immune cells.
The discovery led by the Chicago team may make it possible to predict which patients will respond best to checkpoint inhibitors with a blood test prior to starting treatment, the researchers say. VEGF-C is “easy to measure from a blood sample. If VEGF-C is low, immunotherapy is much less likely to be effective," said team leader Melody Swartz, a professor of molecular engineering at the University of Chicago, in a statement. Although the role of VEGF-C in the body has yet to be fully understood, the study “brings into focus a more comprehensive understanding of the immune microenvironment," she said.