Researchers from Amsterdam UMC have shown how some combinations of cancer treatments work successfully. The article was published today in Nature Reviews Clinical Oncology. “In 1996, we already saw in the laboratory that immunotherapy works better in combination with medication against the formation of blood vessels in tumors. Now, with this literature study, we have a new insight how this works in humans. This knowledge will provide a boost in the development of new treatments against cancer," says oncology researcher Arjan Griffioen of Amsterdam UMC.

In the article, the researchers reviewed existing clinical studies and found ample evidence for a hypothesis they proposed in 1996. “Tumors need new blood vessels and make substances that attract blood vessels to the tumor. This process is called ‘angiogenesis’. Tumors also cause the blood vessels to change in such a way that immune cells can no longer attach to the vessel wall. The reaction of blood vessels to inflammatory processes is completely absent and the tumor is thus protected from the immune system. ” Arjan Griffioen, professor of Experimental Oncology and Angiogenesis, called this phenomenon ‘tumor endothelial cell anergy’. “With medication that counteracts angiogenesis, you overcome this anergy and the immune cells can attack the tumor. In other words, the immune system is empowered to do what it is supposed to do”, says an enthusiastic Prof. Griffioen.

Hypothesis confirmed a quarter of a century later

When Prof. Griffioen and his co-researchers first published the observation that blood vessels do not react to inflammatory processes, they also proposed the hypothesis that anti-angiogenesis therapy can prevent the tumor from escaping the immune system. They reasoned that any immunotherapy should be combined with angiogenesis inhibitors. Now, a quarter of a century later, the study has shown that this hypothesis is correct.

Better treatment combinations against cancer

In 2021, there is a lot of evidence that anti-angiogenesis therapy enhances immunotherapy. More than 90 clinical studies are underway, and five combination therapies have been approved by the U.S. Food and Drug Administration (FDA) as of 2018. Prof. Griffioen explains: “Immunotherapy is a treatment that stimulates our immune system to destroy cancer cells more effectively. When  you combine this therapy with angiogenesis inhibitors, it enhances the immunotherapy. It is a winning combination.” By understanding the ways in which tumors escape immunity and why a patient does not respond to immunotherapy, scientists can design new and improved treatment combinations.

Prof. Griffioen conducted his research with Zowi Huinen, Elisabeth Huijbers and Judy van Beijnum from Amsterdam UMC, and with Patrycja Nowak-Sliwinska from the University of Geneva.

Download the article published in Nature Reviews Clinical Oncology