Some cancer therapies aim at stopping tumor growth by affecting the blood vessels that nurture the tumor mass, while others act on the immune system attempting to eliminate the tumor. Researchers now have discovered that tumor blood vessels and the immune system influence each other's functions, and propose that considering these bilateral effects in cancer therapy might improve outcomes. The study appears in Nature.

"We are trying to uncover a more complete picture of the tumor microenvironment in breast cancer," said corresponding author. "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."

Despite their abundance, tumor blood vessels perform their job poorly because their structure and functions are abnormal. For instance, they do not carry enough blood to the tumor which limits the amount of oxygen and nutrients and creates a harsh microenvironment that can stimulate some cancer cells to escape through gaps in blood vessels and lead to metastasis. Abnormal tumor blood vessels may also interfere with anti-tumor immune cells or drugs attempting to reach the tumor.

Recently, restoring tumor blood vessels' function and structure to normal, a process called vessel normalization, has been considered a promising strategy to improve anti-blood vessel therapies. Vessel normalization can potentially limit or prevent cancer progression and metastasis, and improve the response to immunotherapy, chemotherapy and radiation therapy. However, little is known about how the tumor microenvironment regulates vessel normalization.

By applying their approach of studying the tumor microenvironment as a whole, researcehrs discovered that immune cells called T lymphocytes can promote the process of vessel normalization.

"The reciprocal regulation is also true," senior author 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."

The researchers work suggests that therapies should consider not only, for instance, the presence of immune cells and their activities in the tumor microenvironment, but also the vascular structure of the tumor because it has implications of whether the tumor would be able to respond to immunotherapy.

"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," corresponding author said. "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."

https://www.bcm.edu/news/cancer/immune-system-blood-vessels-cancer

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature21724.html