Targeting Blood Vessels To Improve Cancer Immunotherapy

Targeting Blood Vessels To Improve Cancer Immunotherapy

ArticlePress release
Current Medical News
Cancer & Benign Tumors
+2
Contributed byKrish Tangella MD, MBAMay 24, 2019

EPFL scientists have improved the efficacy of cancer immunotherapy by blocking two proteins that regulate the growth of tumor blood vessels.

Cancer immunotherapy aims to enhance or restore the ability of the patient's immune system -- namely T cells -- to recognize and attack cancer. But tumors use several strategies to fight back immune attacks, making immunotherapy efficacious only in a minority of the patients. For example, they produce blood vessels that block, rather than facilitate, the arrival of T cells. EPFL scientists have now improved the efficacy of immunotherapy against different cancer types by reprogramming the tumor blood vessels. The study is published in Science Translational Medicine, and is featured on the cover of the journal.

Starving tumors

Tumor blood vessels are essential for providing oxygen and nutrients to the growing cancer cells. The laboratory of Michele De Palma at EPFL focused on two proteins, called VEGFA and ANGPT2, which tumors produce to stimulate the growth of new blood vessels. Blocking the actions of VEGFA and ANGPT2 may curb the growth of the blood vessels, limit the provision of oxygen and nutrients, and starve the tumors.

To block both VEGFA and ANGPT2, the EPFL scientists used an antibody called A2V. The team tested A2V in experimental models of breast cancer, pancreatic cancer, and melanoma. They found that A2V provides clear therapeutic benefits, whereas antibodies that block either VEGFA or ANGPT2 alone had more limited efficacy. Importantly, A2V also inhibits metastasis, a condition that is frequently lethal in patients with cancer.

A2V reprograms the tumor blood vessels

Under the influence of VEGFA and ANGPT2, the tumor blood vessels also acquire an aberrant structure that impedes the passaging of T cells, thus limiting the efficacy of immunotherapy. A2V caused the regression of many tumor blood vessels, but some persisted after the therapy.

"One interesting finding was that A2V not only regressed most of the tumor blood vessels, but also reversed the aberrant features of those that had remained, making them similar to normal blood vessels and more permissive to the arrival of anti-tumoral T cells," says De Palma. Indeed, A2V promoted the "extravasation" of activated T cells into the tumors, a process that is required to initiate an immune response against the tumor.

A2V helps checkpoint blockers

Tumors can evade detection and attacks by patrolling immune cells, such as T cells. Tumors accomplish this by expressing certain proteins, called "immune checkpoint ligands." One of these is the protein PD-L1 (programmed death ligand 1), which binds a receptor (PD-1) that is present on the surface of T cells, stopping them from attacking the tumor. A way to circumvent this problem is to use drugs called checkpoint inhibitors. These are usually antibodies that find and bind the immune checkpoint proteins on tumors, thus leaving them open to immune attacks.

The EPFL researchers found that the accumulation of activated T cells around the tumor blood vessels, which was promoted by A2V therapy, also triggered a defensive response: the blood vessels started to produce the checkpoint ligand PD-L1 in an effort to "blind-sight" the attacking T cells. However, the researchers found that it is possible to overcome this setback by blocking the PD-1 receptor. Indeed, an anti-PD-1 antibody further improved the anti-tumoral effects of A2V.

"These data remind us that mechanisms of resistance to anti-cancer therapies are always beyond the corner. While A2V normalized the tumor blood vessels and facilitated the arrival of activated T cells, the anti-tumoral T cells became rapidly suppressed upon their extravasation to the tumor microenvironment," says De Palma.

The study has important implications for cancer immunotherapy. "Our work suggests that certain anti-angiogenic drugs, namely ANGPT2 inhibitors, have more profound effects on tumors than initially thought. Besides targeting the blood vessels, they also help initiate anti-tumoral immune responses, which can be reinforced by immune checkpoint blockade."

Was this article helpful

On the Article

Krish Tangella MD, MBA picture
Approved by

Krish Tangella MD, MBA

Pathology, Medical Editorial Board, DoveMed Team

0 Comments

Please log in to post a comment.

Related Articles

Test Your Knowledge

Asked by users

Related Centers

Loading

Related Specialties

Loading card

Related Physicians

Related Procedures

Related Resources

Join DoveHubs

and connect with fellow professionals

Related Directories

Who we are

At DoveMed, our utmost priority is your well-being. We are an online medical resource dedicated to providing you with accurate and up-to-date information on a wide range of medical topics. But we're more than just an information hub - we genuinely care about your health journey. That's why we offer a variety of products tailored for both healthcare consumers and professionals, because we believe in empowering everyone involved in the care process.
Our mission is to create a user-friendly healthcare technology portal that helps you make better decisions about your overall health and well-being. We understand that navigating the complexities of healthcare can be overwhelming, so we strive to be a reliable and compassionate companion on your path to wellness.
As an impartial and trusted online resource, we connect healthcare seekers, physicians, and hospitals in a marketplace that promotes a higher quality, easy-to-use healthcare experience. You can trust that our content is unbiased and impartial, as it is trusted by physicians, researchers, and university professors around the globe. Importantly, we are not influenced or owned by any pharmaceutical, medical, or media companies. At DoveMed, we are a group of passionate individuals who deeply care about improving health and wellness for people everywhere. Your well-being is at the heart of everything we do.

© 2023 DoveMed. All rights reserved. It is not the intention of DoveMed to provide specific medical advice. DoveMed urges its users to consult a qualified healthcare professional for diagnosis and answers to their personal medical questions. Always call 911 (or your local emergency number) if you have a medical emergency!