Antiangiogenic Therapy Enhances Efficacy of Immunotherapy

A combination therapy triggered the growth of high endothelial venules (HEVs) in mouse models of tumors, resulting in cancer cell death and tumor shrinkage.

In a study published in Science Translational Medicine, investigators demonstrated that combining antiangiogenic and immunotherapy resulted in better therapeutic outcomes in mouse models with tumors by providing openings for white blood cells to infiltrate cancers.

The network of blood vessels is important because it helps regulate and control white blood cell traffic. By preventing the infiltration of white blood cells, it allows the cancer to evade the host’s immune system, according to the authors.

“It was interesting to observe that this combination of immune system activating and antiangiogenic antibodies causes a positive feedback loop,” said investigator Dr Elizabeth Allen. “The result is the growth of specific blood vessels that deliver cancer-fighting immune cells into the tumor. These high endothelial venules are normally found in lymphoid organs such as lymph nodes, where they help transport white blood cells. For the first time, we showed that the growth of HEVs can be therapeutically induced in tumors.”

The anti-PD-L1 therapy can sensitize and increase the efficacy of antiangiogenic therapy. Furthermore, antiangiogenic therapy can improve treatment with anti-PD-L1, particularly when intratumoral HEVs are generated that enhance white cell infiltration, activity, and tumor cell destruction.

The findings indicate that the 2 therapies help stimulate growth of HEVs in pancreatic and mammary tumors, and lead to malignant cell death and a reduction in tumor size.

Next, the investigators plan to examine how intratumoral HEVs are formed and maintained.

“Understanding the underlying mechanisms of the process will contribute to the overarching goal of developing new therapeutic approaches to boosting the immune system in tumors,” concluded investigator Gabriele Bergers.