Research in understanding immunotherapy resistance: A Q&A with Dr. Jason Luke

Question: Why do you believe some cancer patients become resistant to I-O treatment?

Dr. Luke: Research points to two potential reasons for resistance: immune exclusion, when the tumor does something that blocks the ability of the immune system to attack it, and immune exhaustion, when immune cells become dysfunctional and are prevented from doing their jobs in killing cancer. Eventually we hope to identify these mechanisms and translate our findings into specific treatments suited to individual patient needs. 

Question: How is the population of patients resistant to I-O therapy changing?

As the number of patients treated with immunotherapy increases, so does the number of patients with resistant tumors. Given the wide variability of immunotherapy use from adjuvant (after surgery) to first-line treatment after metastasis to post chemotherapy, the types of individuals span all categories of cancer treatment. Researchers are working diligently to understand and address mechanisms of both primary (treatment does not help from the beginning) and acquired (treatment stops working after initial benefit) resistance. 

Question: How can biomarkers potentially help match patients to the appropriate treatments for their specific tumor biology? 

We hope that by identifying potential factors (called “biomarkers”) associated with either the tumor or the immune response we can identify different mechanisms of resistance. An example of this is the “T cell-inflamed” vs “non-T cell-inflamed” paradigm in which T cell-inflamed tumors have a pre-existent immune response that can be augmented with immunotherapy. As these biomarker efforts become more specific, we hope to identify markers that will help us apply treatments in a personalized approach to avoid treatment resistance.  

Question: How close would you say the field is to identifying some of these mechanisms of resistance?

We are all working as fast as possible. While it is hard to gauge when a scientific breakthrough may occur, the field continues to advance with new research each day. As more patients become resistant, it also provides us with an opportunity to build on our understanding for what is happening. For example, at the University of Chicago, we are actively gathering tumor biopsies and blood draws upon resistance to help us study why patients become resistant. Once we have a better understanding of why patients become resistant to treatment and the biomarkers associated, we can hopefully design treatments in such a way that will improve their response.