Harnessing the immune system to combat cancer: A Q&A with Postdoctoral Fellow Dr. Michael Dahabieh

Immunotherapies have been a game-changer for cancer.

These powerful treatments work by bolstering the immune system’s ability to detect and kill cancer cells, but they don’t work for everyone or for all cancers. Van Andel Institute’s Michael Dahabieh, Ph.D., a postdoctoral fellow in the lab of Russell Jones, Ph.D., aims to improve these promising treatments by identifying new ways to re-energize immune cells in their battle against cancer. His research recently earned him a prestigious Pathway to Independence Award (K99) from the National Cancer Institute of the National Institutes of Health to support the next stages of this important work.

In this Q&A, Dahabieh shares more about his research, how the award will support him and what motivates him in the lab every day.

What is the big problem you’re trying to solve with your research?

MD: Our immune system has special cells called CD8 T cells that usually do a good job of finding and killing things that don’t belong in our body, like virus-infected cells or cancer cells. But sometimes infections or cancers stick around anyway. When that happens, T cells can get “exhausted,” which means they stop working as effectively.

Immunotherapies try to wake up these “exhausted” CD8 T cells by blocking certain “brakes” on the immune system. Normally, these “brakes” prevent immune cells from accidentally attacking healthy cells; however, cancer cells take advantage of this braking system to switch off T cells and evade immune attack. Immunotherapies have been life-changing for some patients, but many still don’t respond. That’s the big problem we’re working to solve by focusing on T cell exhaustion.

How will this award help you address the problem?

MD: During my postdoctoral work in Dr. Rusty Jones’s lab here at VAI, I discovered a new target called PTGIR that might help re-energize “exhausted” T cells. PTGIR is an immune checkpoint, a type of protein “brake” that helps regulate the number and cancer fighting powers of T cells. In cancer, immune checkpoints can help cancer cells hide from the immune system. Unlike most immune checkpoints, which involve proteins binding to proteins, PTGIR binds to a fat-like molecule called prostacyclin. When this interaction happens, it drives T cells into exhaustion.

In a recent study, when we removed PTGIR from T cells, those T cells became better at fighting infections and cancers.

This award will allow me to:

• Investigate whether cancer cells themselves make prostacyclin
• Better understand how PTGIR and prostacyclin push T cells into exhaustion
• Explore new targets that could potentially block PTGIR and prevent prostacyclin from binding to immune cells, giving “exhausted” T cells a second chance at fighting cancer

What is the most exciting thing about your research?

MD: What excites me most is when the data lead us somewhere unexpected. Following the evidence — rather than assumptions — led me to identify PTGIR as a brand new immune checkpoint. It’s especially thrilling when we uncover something nobody has described before and then realize it may be a key piece of a puzzle we thought we already understood. That sense of discovery and possibility is what drives me every day.

Funding acknowledgement

Research highlighted in this publication was supported by the National Cancer Institute of the National Institutes of Health under award no. K99CA293261 (Dahabieh). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.