Beth A. Helmink, MD, PhD
Assistant Professor, Department of Surgery - Washington University in St. Louis
A Novel Model for Studying the Intersection of Tumor Immunity and Autoimmunity
can autoimmune mice help us understand how cancer manipulates the immune system?
Dr. Helmink hopes to better clarify how a tumor hides itself from the immune system and if there are ways to allow immunotherapy to be more effective. Our immune system relies on the ability to protect what it recognizes as part of the body and to attack what it recognizes as foreign. As cancer grows, it becomes less like the rest of the body and more recognizable as other. However, the immune system doesn’t recognize all of the tumor as foreign at once, allowing “immunoediting,” where a tumor evolves to have less of the cells that excite the immune system and results in a tumor that the immune system can no longer recognize. This is one of the ways in which a tumor “outsmarts” the immune system. Hijacking immune checkpoints is another way tumors elude immune system attacks; many immunotherapies are focused on inhibiting immune checkpoints. Blocking these checkpoints can be effective in fighting cancer but can also lead to autoimmune diseases that significantly limit their usefulness. We need to understand how tumors control immune checkpoints without fully upsetting the immune system and leading to autoimmune disease.
Dr. Helmink has developed a model where tumors are in introduced to mice with auto-immune disease; immunotherapy is not effective in these mice, although one might assume that the immune system would be particularly primed to react. Dr. Helmink plans to use this unique model to see why: is strong immunoediting occurring or does the auto-inflammatory state actually express a different “checkpoint molecule” with a different relationship to autoimmune disease? She will characterize many different tumor lines that show varying sensitivity to immunotherapy and then determine why and how these different tumor lines are resistant to immunotherapy. She hopes to better understand how Immunity and autoimmunity are linked, and to find ways to leverage their interrelatedness to design better cancer immunotherapies.