Turning On and Off T Cells in the Body Could Improve Breast Cancer Outcomes

Oct 21, 2021 | Research

Lisa Coussens, Ph.D., has devoted more than 20 years to researching ways to leverage the immune system in the body to treat breast cancer.

Dr. Coussens was recently named a Komen Scholar, where she is part of an advisory group of distinguished leaders in breast cancer research, clinical practice, public health, advocacy and other relevant fields. This group provides expertise to Susan G. Komen on research and programs related to education, advocacy, community health and global outreach.

She spoke to Komen about her research and what the last 20 years of discoveries have taught her.

Q: Let’s start with the basics. What are T cells and why are they important in cancer research?
A:
T cells and other immune cells are there to protect your body and aid in healing. Immune cells respond to damage – a bacterial infection, a viral infection, a paper cut – whatever the body is experiencing.

We’ve always known, through decades of immunology research, that T cells are very important in the fight against disease, including cancer. But what we did not know was how to harness T cell activities, or how those T cells were dysregulated in cancers. My lab has been studying the recruitment of other types of immune cells, e.g., macrophages (white blood cells that stimulate immune system cells), into early-stage tumors. We’ve learned that some macrophage activities are hijacked in early cancers. Instead of eradicating would-be tumor cells, they instead help the early tumor cells to survive by creating environments that are favorable for them to live in. We’ve also learned that macrophages turn off the cytotoxic, or the tumor cell killing, activity of T cells.

Q: It sounds like being able to stop that process and unleash the T cells to fight tumors, from the beginning, is really key in killing tumors.
A:
Exactly. Susan G. Komen provided me with a grant that will take our basic understandings from the lab even further – to really understand how macrophages can influence T cell function, but also specifically which T cell populations in tumors are regulated by macrophages. If we can understand the ways that macrophages are turning off select types of T cells, we can then target and prevent this directly with therapy. Another goal of this grant is to better understand which subsets of T cells respond to therapies that interfere with how macrophages communicate with T cells. This way, we can learn how T cells are being controlled and selectively turn on the T cells subsets that are able to fight cancer.

Q: Turning T cells on and off sounds like a simple enough concept, but we know that very few things in cancer research are simple. How would that on/off process work?
A:
There are a couple different ways. One way is using a drug, for example a chemical or antibody-based therapy, that selectively blocks the signals from macrophages to T cells. Another way is a drug that blocks those signals from being understood by the T cell, so that they can do their job and kill tumor cells without being turned off.

Q: As you look ahead, where does your research take you and what kinds of discoveries are you hoping to make?
A:
Ten years ago, we found that it was possible to therapeutically target macrophages and reduce cancer burden. Some of these therapies are now FDA-approved for slowing cancer progression in patients with a rare tumor type. Now, numerous macrophage-targeted therapies are now in clinical trials being tested in combination with chemotherapy or radiation therapy, as well as with other forms of immune therapy aiming to activate T cells. We need to understand how to combine them in cancer patients, determine which cancer types are likely to respond, and at which stage of cancer these combination approaches are most impactful for patients.

Before my career finishes, I hope to see effective macrophage-targeted therapies in the clinic. My hope is that we understand how best to utilize them to improve outcomes and survival for cancer patients, and to identify which therapies have the greatest impact for improving patients’ quality of life and extending their longevity.

Q: When we hear about a ‘cure’ for cancer, we often hear that teaching the body’s immune system to recognize and kill tumors from the start could be one cure. Those learnings started in biology labs so what does the research field look like today, and what would help it grow and thrive?
A:
Progress made in the last 20 years toward understanding how to harness the immune system to fight cancer has been achieved through many laboratories around the world working toward a common goal, but also willingness to collaborate and share information. Collaboration is key in my opinion. I invite students and fellows from around the globe to my lab to learn methods that we have developed, and my students go to other labs to learn how other people do things – this kind of collaboration makes scientific research much more fun at all levels of professional development.

Foundations like Susan G. Komen are critical. My research on macrophages was far from mainstream cancer science 20 years ago, but Komen funding allowed us to do groundbreaking research and invest in ideas that have a strong possibility to impact patients.

Q: What impact do you hope to have while serving as a Komen Scholar?
A:
I’m looking forward to assisting Komen with its grant portfolio and reviewing grants from young scientists. I am excited to help identify the science that needs to be invested in that might, on the outset, appear to be just crazy but could represent a paradigm shift and open up entirely new areas of study.

I’m also looking forward to working with Komen’s patient advocates. The degree to which we can charge them and make them excited about working with researchers, for them to keep us real, that’s 100 percent critical for mission success. We can work collaboratively with the advocates, and together we can bring our excitement about research to educate patients about what their options are, why it’s important to participate in clinical trials, why it’s important to be an advocate and work with researchers. That’s a lot of success, as far as I’m concerned.

*Dr. Coussens is a Professor and Chairwoman of the Cell, Development & Cancer Biology Department, the Hildegard Lamfrom Endowed Chair in Basic Science and the Associate Director for Basic Research at the Knight Cancer Institute of Oregon Health & Science University.