The introduction of immune checkpoint inhibitor therapy has revolutionized the treatment of metastatic melanoma patients and has meaningfully extended overall survival for many. However, a persistent problem is the development of immune-related adverse events (irAEs) in a number of patients. Effective treatment of these irAEs is critical to the safe administration of checkpoint inhibitor (CPI) therapy. There is an emerging body of evidence that implicates a rampant upregulation of T cell activity as a basis for the toxicity in these patients. Therefore, a better characterization of the immunology of irAEs is important for understanding the reasons for irAE development. As one of the more common and severe irAEs seen in clinical practice, colitis presents a unique challenge for clinicians managing patients on immunotherapy. Using validated genomic and bioinformatic approaches, we seek to interrogate peripheral blood T cell populations seen in patients on dual CTLA4/PD1 immunotherapy that develop biopsy-confirmed CPI colitis. A better understanding of the underlying immunology may help with the development of mechanism-driven methods for better prevention, for treating toxicities and improving patient outcomes on checkpoint inhibitor therapy.
|Effective start/end date||2/1/19 → 2/1/20|
- Melanoma Research Foundation (Letter 2/13/19)