Identifying Marker Genes to Predict Immune-Related Adverse Events in Patients Receiving Anti-PD-1 Immunotherapy
Name: Nicholas Beatty
School: Vagelos College of Physicians and Surgeons, Class of 2023
Mentor: Syed Bukhari, PhD and Annette Wu, MD, MPH, PhD
Abstract
Anti-PD-1 therapy is an effective cancer treatment that inhibits tumor growth by activating T-cells. However, one in four patients who receive this therapy develop immune-related adverse events (irAEs), or autoimmune reactions manifested as cardiomyopathy, thyroiditis, pneumonitis, etc. We hypothesized that this autoimmune outcome is in part due to predisposing genetic alterations and that T-cell gene expression may reveal patients’ genetic immune profiles, including marker genes which may predict a patient’s predisposition to developing an immune-related adverse event. To find these marker genes, we performed single cell RNA analysis on the cells of eight patients (deemed eligible out of 38 total) who received anti-PD-1 therapy for lung cancer, both before they either developed post-therapy rheumatoid arthritis or thyroiditis, or did not, and analyzed the differences in T-cell gene expression in these patients. We found multiple T-cell genes that differed in expression between those who developed rheumatoid arthritis or thyroiditis and those who did not, including apoptotic transcription factors, JUND and FOS. These identified genes may be of significant use in predicting an individual patient’s risk of developing an immune-related adverse event as a result of anti-PD-1 therapy and may inform future healthcare providers deciding between cancer treatment options.