Understanding how T cells learn to fight cancer

What biomedical issue did you address in your research, and what did your studies find?

My research focused on understanding how the immune system develops T cells that help fight cancer. Even though recently introduced cancer immunotherapies have transformed cancer treatment and can lead to remarkable tumor regression, not all patients experience long-term control of their disease. Greater understanding of how the body's anti-tumor immune responses develop may help improve patient care.

My thesis work asked whether PD-1, a molecule that can regulate T-cell activity in tumors and other parts of the body, affects T cells early in their development. T cells develop in the thymus, an organ that gradually shrinks with age but produces new T cells throughout life. In a preclinical model, I studied what happens when PD-1 is removed from developing CD8 T cells, a type of immune cell that can recognize and kill cancer cells.

Using a combination of innovative technologies, including single-cell and T-cell receptor sequencing, along with models of cancer and tests of immune cell function, I found that PD-1 helps shape how developing CD8 T cells acquire cancer-fighting abilities. When PD-1 is absent, thymic CD8 T cells gain stronger cell-killing capacity and contribute to an enhanced immunity against cancer. These findings, published in Nature Communications, suggest that immune checkpoints like PD-1 can shape the immune system earlier than previously appreciated, opening new possibilities for how a long-lasting benefit of immunotherapy can be achieved. 

What aspects of your training at Mayo helped you grow as a scientist and as a thinker?

As someone interested in patient-oriented translational immunology, I benefited from Mayo's close connection between research and clinical care. I had the opportunity to work with clinical samples that had been donated by people with and without cancer, and to collaborate with physicians and clinician-scientists on important clinical questions.

I am especially grateful for the mentorship of Dr. Haidong Dong, whose pioneering work in cancer immunology has shaped the field. His lab's motto, "Be happy, be safe, and then be productive," reflects the supportive, collaborative environment he creates in the lab and beyond.

What's next?

I will continue my academic training as a postdoctoral research associate in the Department of Laboratory Medicine and Pathology at the University of Minnesota. My long-term goal is to pursue an academic career where I can combine impactful research with meaningful mentorship and teaching. I hope to continue studying how the immune system can be harnessed to improve human health while also supporting and training the next generation of scientists.

This article was written by Meredith Lilley, a Ph.D. candidate in Neuroscience at Mayo Clinic Graduate School of Biomedical Sciences.