Raising Hope

Author(s):

Kyle Doherty

Grant winner Tyler Miller, MD, PhD, outlines innovative plans for glioma research.

Tyler Miller, MD, PhD

The Brain Tumour Charity, a nonprofit organization dedicated to funding brain cancer research worldwide, recently announced that Tyler Miller, MD, PhD, a clinical pathologist and research fellow at Dana-Farber Cancer Institute in Boston, Massachusetts, had received a grant of £600,000 ($758,000) as a Junior Fellow in the charity’s Future Leaders program.

With this grant, Miller aims to kick-start his research into reprogramming immune cells to make immunotherapy effective in gliomas.

The Brain Tumour Charity offers up to £1.8 million ($2,280,000) in funding over 12 years, providing clinicians with the support needed to set up their own laboratory.

“I'm incredibly grateful for the charity, as well as their fundraisers and the donors and the advocates for arranging their research,” Miller said in an interview with Oncology Fellows of the November 2023 announcement. “The only way that we are going to create a breakthrough treatment for patients with brain tumors is through research. But research is expensive. It takes organizations like The Brain Tumour Charity, as well as the friends, families, and patient advocates, to raise that money and enable us to do this research. There is not enough money in the government alone to do the types of innovative research that are going to create the type of breakthrough that we want for these patients.”

In the interview, Miller discussed his plans for the grant, his unique research focus on glioblastoma, and what inspired him to pursue brain cancer research as his career.

Oncology Fellows: Congratulations on receiving this grant from The Brain Tumour Charity. What does this achievement mean to you?

Miller: The Brain Tumor Charity Future Leaders program is a very innovative program that starts supporting researchers right out of graduate school when they are doing their postdoctoral research. This is a critical time for researchers as they try to [gain] independence, and having that support gives us a lot of freedom to explore areas that we want to explore and maybe do some riskier but high-reward experiments than we would have been able to do otherwise.

The Future Leaders program itself has stages. You start with a 3-year postdoctoral fellowship, then there is the junior fellowship, which is the fellowship I just received [Dr Spencer Watson, in Switzerland, and I] are the first two people to receive the Junior Fellowship for this program, which allows us to transition into independence. For me, that means having the ability to go out and get an independent faculty position and start up my own lab with this funding. This enables us to kick-start types of experiments and the type of research that I want to do in my own independent lab.

Then, there is one more step. After this 4-year junior fellowship, there is a 5-year senior fellowship that we can apply for. That really supports the next stage of your career as you go from early-career scientist to an established principal investigator who can hopefully make an even bigger impact through the research.

What are your plans for the grant and what impact will it have on brain cancer research?

The whole goal of my research program is to figure out how we can make immunotherapies more effective for patients with brain tumors. The plans for this grant are to use this funding to figure out how we get around the suppressive tumor microenvironment.

[There are] myeloid cells in the tumor that are typically supposed to recruit additional immune cells, such as T cells, to come in and kill the tumor. However, the brain tumor itself has figured out a way to transform those cells into being procancer and they actually inhibit T cells and other immune cells from coming in and killing the tumor cells. The goal of this grant is to figure out how we get around that immunosuppression by these myeloid cells that are in the tumor suppressing the T cell and the overall immune cell response.

What makes your research focus unique?

A lot of research in glioblastoma has focused on the cancer cells themselves. How do we find vulnerabilities within the cancer cells that we can target? Many of the targeted therapies that we have tried target the cancer cells directly. Temozolomide is the chemotherapy that is used as the standard of care and targets the cancer cells. Radiation targets the cancer cells and, with surgery, the goal is to get rid of the cancer cells.

I'm focused on targeting the immune cells that are in the tumor to transform them so that they can attack the tumor cells. The reason this approach is innovative, and the reason I believe it is our best shot at a cure for patients with glioma or glioblastoma, is that this cancer is incredibly heterogeneous. All of the targeted therapies that we have tried have failed because the tumor cells themselves are so heterogeneous that if you target one set of the cancer cells, the rest of them sort of just get around that—[they] grow up, and replace the lost cancer cells.

By targeting the immune system so that it can fight the tumor cells, it has a better shot of managing the heterogeneity, and it can target the whole tumor and adapt as the tumor adapts. Rather than having a single target on the cancer cells, the immune cells can target many targets within the cancer cells.

What initially inspired you to focus on glioblastoma and brain cancer?

When I was an undergraduate, I did research at Ohio State University on breast cancer. It was a great learning experience as my first taste of cancer research. But when I transitioned to graduate at Case Western Reserve University School of Medicine, I wanted to figure out how I could make the biggest impact on patients through my research. I decided I wanted to focus on a cancer where patients didn’t have any good options currently and were the patients who needed the most help.

I thought about a couple of different cancers, including pancreatic cancer and brain cancer. Dr Jeremy Rich was a physician-scientist and mentor at the medical school who had a great brain tumor research lab at Cleveland Clinic, just down the street. He was active in the clinic seeing brain tumor patients and was running a cutting-edge research lab. I jumped in his lab and focused on brain cancer, with the realization that if I found something in the lab that was promising, it was quite easy to translate that into a clinical trial and try to make an impact. These patients have no good options for treatment at the moment.

Since I started in that space, I have had lots of experiences with patients and their families, as well as my own family members and friends. Once people know that you are in this space, they seek you out to get advice and help. I helped a lot of people and their families get through their disease.

It's a terrible disease; there are no good therapies and the therapies we do have are debilitating in many ways for patients. The quality of life of these patients is [low] for many of them. They really need [more effective treatments].

Right at the end of my PhD, [the father of] one of our other MD/PhD students who was in the lab with me was diagnosed with glioblastoma. Here is a guy who I looked up to a lot and was a mentor of mine, and we both were studying glioblastoma at one of the best places in the world to study glioblastoma that could have sent him anywhere, done anything to help them, and he had no options. We knew what was going to happen, and you just felt helpless. That type of thing [motivates you] to stay in the space.

When I came to Dana-Farber Cancer Institute, I had the opportunity to reset, and I could have changed my focus area. But after having had those experiences, this is something that I am very passionate about: figuring out how we create better therapies for these patients and raising hope for these families.