There are cancer treatments that work by disrupting the growth of blood vessels that support tumors; others aim to use the immune system as a way to attack the tumor itself. New work shows that these two systems, tumor blood networks and the immune system, affect one another. The Baylor College of Medicine researchers have suggested that cancer treatments should take this relationship into account, and that it may lead to an improvement in cancer therapeutics. Learn more about the work, which was reported in Nature, from the following video.
“One of the characteristics of successful cancerous tumors is their ability to trigger the formation of new blood vessels, a process called angiogenesis, to supply oxygen and nutrients to the growing cell mass,” said corresponding author of the report Dr. Xiang Zhang, an Associate Professor of Molecular and Cellular Biology at the Lester and Sue Smith Breast Center at Baylor. “Therapies that aim at blocking angiogenesis to starve the tumor can retard its growth; however, they can also have an undesired effect, tumor progression and resistance to treatments.”
Zhang and colleagues decided to study the microenvironment of the tumor to learn more. “We are trying to uncover a more complete picture of the tumor microenvironment,” said Zhang. “The tumor environment includes tumor cells and other types of cells that are recruited to the tumor mass and help the tumor grow. Scientists have divided those cells into subpopulations and studied them separately. We think that for a more complete understanding of the entire tumor microenvironment we have to study it with all its cell types together. Here, we applied this approach and discovered for the first time connections between tumor blood vessels and the immune system.”
Tumor blood vessels are abundant, but inefficient because they’re abnormal. A disrupted structure means functions are not performed well. That creates a harsh microenvironment for the tumor, which can actually trigger the escape of some cancer cells, and metastasis. These circumstances also exacerbate drug deliver and effectiveness.
One new treatment avenue involves correcting the structure and function of the tumor’s blood vessels, called vessel normalization. It aims to prevent or reduce cancer metastasis and progression in addition to improving the effectiveness of treatments. There is little known about how the microenvironment affects vessel normalization.
Through the analysis of the tumor microenvironment as a whole, Zhang’s team found that T lymphocytes, cells of the immune system, can promote vessel normalization. “The reciprocal regulation is also true,” Zhang said. “If we change the structure of the vasculature of the tumor toward vessel normalization, then we can also stimulate T cells to infiltrate the tumor. This bidirectional regulation between blood vessels and the immune system had not been elucidated before.”
“Both anti-blood vessel therapies and immunotherapies have been used in the clinic and have different degrees of success,” Zhang explained. “For instance, immunotherapy has been successful in some types of cancer such as melanoma and lung cancer, which are very aggressive cancers that did not have effective treatment until these therapies came along. However, there are still many patients who do not respond to this type of therapy. Similarly, from the anti-blood vessel therapy we know that many attempts have not been as successful as anticipated, and we have not been able to understand why.”
“Our finding suggests that anti-cancer therapies toward the blood vessels most likely influence the anti-tumor immune response, and vice-versa. Therefore, there is a possibility that by combining the therapies we can achieve better outcomes,” Zhang continued. He noted however, there is work to be done.
“However, we are still far from having practical clinical solutions. We hope that our work will provide some therapeutic theoretical basis for those researchers using the two different therapies to collaborate and look at each other’s biomarkers and therapeutic strategies,” he concluded.