The blood vessels that feed tumors are often abnormal—plagued by gaps that allow cancer cells to escape and spread through the body, or unable to sustain enough blood flow to deliver cancer-killing drugs to tumor cells. That’s why some cancer researchers are pursuing a new approach called “vessel normalization,” which is a strategy centered around restoring normal function to tumor blood vessels.
Now scientists at Baylor College of Medicine have found a powerful tool to promote vessel normalization: immune cells known as T lymphocytes. They have discovered that tumor blood vessels and T lymphocytes influence each other. Gaining a better understanding of this cross-communication could improve cancer treatments, the researchers suggest in the journal Nature.
Inhibiting the ability of tumors to form blood vessels is at the center of some cancer drugs, including Genentech’s Avastin. “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," said co-author Xiang Zhang, an associate professor of molecular and cellular biology and the Lester and Sue Smith Breast Center at Baylor, in a press release.
Zhang and his team discovered that when they normalized the structure of blood vessels that feed breast tumors, they could encourage T cells to invade the tumors. This could have implications not only for improving anti-angiogenesis drugs, but also for developing immuno-oncology treatments that might work against several tumor types, Zhang said.
"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,” he said in the release. “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."
Indeed, Avastin was initially approved by the FDA to treat breast cancer, but the agency revoked that approval in 2011 after an advisory committee to the agency questioned the efficacy of the anti-angiogenesis drug in that tumor type. Avastin is still approved to treat several tumor types, including colorectal cancer, glioblastoma and some types of ovarian and cervical cancer.
As for immuno-oncology drugs, several research efforts are underway to broaden their usefulness beyond melanoma and lung cancer. Last fall, for example, scientists at the Wistar Institute published research showing that an emerging class of treatments known as bromodomain and extraterminal domain inhibitors seem to work against ovarian cancer cells by suppressing the activity of PD-L1—an immune “checkpoint” that prevents T cells from attacking tumors. More recently, Emory scientists demonstrated that even after the related checkpoint PD-1 is blocked, T cells need additional stimulation to proliferate and to launch an effective immune response against cancer.
Baylor’s Zhang suggests that combining blood-vessel-targeted therapies with immuno-oncology approaches could be promising in some cancers, though he concedes there is still plenty of work to do before his insights can be translated into practical therapies: "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."