Myocardial Expression of PD-L1 as a Marker of Poor Prognosis in Immune Checkpoint Inhibitor–Associated Myocarditis | JACC: CardioOncology

0:00My name is Adrian Chen. I am a Sarnath Cardiovascular Research Fellow at UCSF, studying under Dr. David Moslehi at University of California, San Francisco, in the section of Cardi oncology and immunology. I will be discussing the study entitled myocardial expression of PDL1 as a marker of poor prognosis and immune checkpoint inhibitor associated myocarditis by doctors Emeyoga and colleagues from the National Cancer Center Hospital East and the University of Sacuba in Japan. ICI myocarditis remains one of the most feared complications of cancer and immunotherapy and there's a growing need to identify high-risk patients that need accelerated therapy. In this study, a myocardial expression of program death receptor ligand 1 or PDL1 was evaluated as a biomarker of disease severity and 20 patients with biopsy proven ICI myocarditis in Japan. PDL1 levels were quantified by immunohistochemistry and patients were stratified using an 8% cutoff into high and low expression groups. Seven patients had high PDL1 expression and 71% of them experienced a 30-day adverse cardiac

1:03event compared to just 8% in the low expression group corresponding to a hazard ratio of 10.6. The high PDL1 group also had markedly higher component levels, prolonged QRS duration, and over 10 fold greater myocardial T cell and macavage infiltration. Interestingly, PDL1 expression decreased with longer time to biopsy and was lower in patients who had received corticosteroids. PDL1 is not normally expressed in the heart, but it upregulated during inflammation to limit immune injury. In ICI myocarditis, however, this protective mechanism is overwhelmed, making PDL1 a marker of the disease severity instead. Quantitative PDL1 staining may therefore provide a useful tool risk stratification at diagnosis. Looking ahead, circulating soluble PDL1 or PDL1 targeted pet imaging could offer non-invasive alternatives, expanding access beyond centers that perform biopsies. We congratulate doctors Imeyoka, Tijiri, and colleagues on this important contribution to