Nav: Home

Double agents: Vessels that help cancers spread can also boost immune therapies

September 13, 2017

In a surprise finding, an international research team from the University of Chicago, the University of Lausanne, and the Swiss Federal Institute of Technology in Lausanne has discovered that the lymphatic vessels, often blamed for enabling cancer cells to spread from a primary location to many other sites, have a flip side.

Lymphatics can expand around and into a tumor - a process known as lymphangiogenesis. This process has long been associated with a cancer's ability to spread to new locations.

But a team led by Melody Swartz, PhD, the William B. Ogden Professor in Molecular Engineering at the University of Chicago, found that in patients being treated with checkpoint inhibitors - drugs such as ipilimumab or nivolumab that help activate an immune response against the tumor - lymphangiogenesis can strongly enhance the effects of cancer immunotherapy. It boosts the immune system's primary anti-cancer tool, T cells, enabling them to infiltrate tumors and kill cancer cells.

The study, piloted by first authors Manuel Fankhauser and Maria Broggi and published in the 13 September, 2017, issue of Science Translational Medicine, suggests that physicians may predict - with a simple blood test before starting treatment - which patients are most likely to benefit from cancer immunotherapy, at least in melanoma patients. Currently, only a minority of patients actually benefit from such therapies. Moreover, it has the potential to lead to new therapeutic strategies to make cancer immunotherapy more effective for more patients.

"Our study presents a completely unexpected role for the lymphatic system in cancer therapy," explained Swartz.

Lymphangiogenesis is driven in part by a chemical messenger, vascular endothelial growth factor-C (VEGF-C), which has long been associated with metastasis and poor patient prognosis, and can also promote immune suppression in the tumor microenvironment.

"VEGF-C was always considered bad for cancer patients," Swartz said. "We thought that blocking VEGF-C would help boost immunotherapy by removing some factors that suppress the abilities of T cells to kill tumor cells. That was our original hypothesis." But their studies in mice, followed by human data obtained from two clinical trials for melanoma patients, changed their thinking.

"It was exciting to get such surprising results," Swartz said. "And the translational implications are even more exciting than if our hypothesis had been correct."

In both trials, the results showed that VEGF-C levels in the blood before immunotherapy "not only predicts the magnitude and quality of immune responses raised by a cancer vaccine but also stratifies long-term patient responses to combined checkpoint blockade and further strengthens the case for investigating the use of serum VEGF-C as a predictive biomarker for immunotherapy candidates," the authors wrote.

"Before the trials began, we took blood samples," Swartz said. "We measured dozens of factors, but nothing else correlated, not VEGF-A, VEGF-D or other growth factors, only VEGF-C."

"The difference was really striking," Swartz said. Almost all of the patients with higher than average VEGF-C levels in their blood responded to immunotherapy. This not only resulted in eradication of the primary tumors, it also encouraged T cell infiltration into metastatic tumors and resulted in long-term protection.

This could become a useful biomarker, Swartz suggested. "It's easy to measure from a blood sample. And it can predict who is likely to respond. If VEGF-C is low, immunotherapy is much less likely to be effective."

The authors noted 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 those limitations, this study "brings into focus a more comprehensive understanding of the immune microenvironment," Swartz said.

"We now appreciate the numerous mechanisms of immunosuppression that a T cell-inflamed tumor develops to survive, including lymphangiogenesis," the authors conclude. "But when the scales are tipped toward activating factors dominating over suppressive ones, as is the case with immunotherapy, these T cells become robust participants in antitumor immunity."

-end-

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

University of Chicago Medical Center

Related Cancer Articles:

Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy
Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, Conn., USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
UH Cancer Center researcher finds new driver of an aggressive form of brain cancer
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age.
UH Cancer Center researchers develop algorithm to find precise cancer treatments
University of Hawai'i Cancer Center researchers developed a computational algorithm to analyze 'Big Data' obtained from tumor samples to better understand and treat cancer.
New analytical technology to quantify anti-cancer drugs inside cancer cells
University of Oklahoma researchers will apply a new analytical technology that could ultimately provide a powerful tool for improved treatment of cancer patients in Oklahoma and beyond.
Radiotherapy for lung cancer patients is linked to increased risk of non-cancer deaths
Researchers have found that treating patients who have early stage non-small cell lung cancer with a type of radiotherapy called stereotactic body radiation therapy is associated with a small but increased risk of death from causes other than cancer.
Cancer expert says public health and prevention measures are key to defeating cancer
Is investment in research to develop new treatments the best approach to controlling cancer?
UI Cancer Center, Governors State to address cancer disparities in south suburbs
The University of Illinois Cancer Center and Governors State University have received a joint four-year, $1.5 million grant from the National Cancer Institute to help both institutions conduct community-based research to reduce cancer-related health disparities in Chicago's south suburbs.
Leading cancer research organizations to host international cancer immunotherapy conference
The Cancer Research Institute, the Association for Cancer Immunotherapy, the European Academy of Tumor Immunology, and the American Association for Cancer Research will join forces to sponsor the first International Cancer Immunotherapy Conference at the Sheraton New York Times Square Hotel in New York, Sept.

Best Science Podcasts 2017

We have hand picked the best science podcasts for 2017. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: Radiolab

Oliver Sipple
One morning, Oliver Sipple went out for a walk. A couple hours later, to his own surprise, he saved the life of the President of the United States. But in the days that followed, Sipple's split-second act of heroism turned into a rationale for making his personal life into political opportunity. What happens next makes us wonder what a moment, or a movement, or a whole society can demand of one person. And how much is too much?
Now Playing: TED Radio Hour

Future Consequences
From data collection to gene editing to AI, what we once considered science fiction is now becoming reality. This hour, TED speakers explore the future consequences of our present actions. Guests include designer Anab Jain, futurist Juan Enriquez, biologist Paul Knoepfler, and neuroscientist and philosopher Sam Harris.