Megan Burger, PhD

Lung cancer is the second most common cancer type and the leading cause of cancer-related deaths worldwide. Better treatments and biomarkers that predict patient response are greatly needed to reduce the impact of this terrible disease. Cancer immunotherapies that activate killer T cells of the immune system to seek out and eliminate cancer cells represent a promising new treatment approach for lung cancer. These therapies elicit curative responses in some patients and have been FDA-approved across multiple lung cancer types, including as a first-line therapy. Still, most patients do not benefit from this approach. We aim to understand why and identify ways to improve immunotherapy design to reach more patients. Our studies will use sophisticated mouse models of lung adenocarcinoma, the most common type of lung cancer, to understand what controls whether T cells can kill cancer cells and identify new immunotherapy approaches that improve T cell function.

Update:

Our work is focused on understanding how expression patterns of neoantigens – molecules generated by tumor cells that trigger immune responses -- in lung tumors regulate T cell recognition and killing of cancer cells. We have discovered that when multiple neoantigens are present in tumors, T cells compete with each other, which limits the effectiveness of their ability to fight cancer. These insights could help identify which types of neoantigen profiles would benefit most from personalized cancer vaccines, potentially in combination with immune checkpoint blockade therapy. Surprisingly, our studies show that prolonged use of immune checkpoint blockade therapy can lead to dysfunction in CD8 T cells (a type of white blood cell that kills cancer cells). We're now exploring whether shorter treatment periods might work better and could be combined with vaccination to boost their effectiveness against lung cancer.