Myocardial Expression of PD-L1 as a Marker of Poor Prognosis in Immune Checkpoint Inhibitor-Associated Myocarditis

Immune checkpoint inhibitors (ICIs) have improved cancer outcomes but are associated with severe immune-related adverse events, including myocarditis. PD-L1 plays an important role in immune regulation and homeostasis. Myocardial PD-L1 up-regulation has been reported in ICI-associated myocarditis; however, its clinical significance and prognostic value remain unclear.

This study sought to investigate the association between myocardial PD-L1 expression and ICI-associated myocarditis severity and prognosis.

Twenty consecutive cases of biopsy-proven ICI-associated myocarditis were analyzed. Endomyocardial biopsy specimens underwent immunohistochemical staining for PD-L1, and patients were categorized into high (≥8%) or low (<8%) PD-L1 expression groups. Clinical presentation and the incidence of major adverse cardiotoxic events, defined as a composite of severe heart failure, severe arrhythmia, or cardiac death, were compared between groups.

The median follow-up time for the cohort was 189 days (Q1-Q3: 88-308 days). The absolute risk of 30-day major adverse cardiotoxic events was significantly higher in the high PD-L1 group (n = 5 of 7 [71.4%], 95% CI: 29.0%-96.3%) than in the low PD-L1 group (n = 1 of 13 [7.7%], 95% CI: 0.2%-36.0%; P = 0.007). The median peak normalized troponin level (× upper limit of normal) was significantly higher in the high PD-L1 group than in the low PD-L1 group (662 [Q1-Q3: 204-855] vs 64 [Q1-Q3: 26-108]; P = 0.010). Patients in the high PD-L1 group also had longer QRS duration on electrocardiography (124 ms [Q1-Q3: 108-131 ms] vs 96 ms [Q1-Q3: 90-102 ms]; P = 0.021). Myocardial inflammatory cell infiltration was greater in the high PD-L1 group, with higher CD3⁺ T cell infiltration (35.9% [Q1-Q3: 25.8%-42.8%] vs 2.6% [Q1-Q3: 0.6%-5.8%]; P = 0.007) and higher CD68⁺ macrophage infiltration (15.2% [Q1-Q3: 10.2%-21.1%] vs 1.23% [Q1-Q3: 0.4%-2.3%]; P = 0.007).

High myocardial PD-L1 expression is associated with greater disease severity and a higher risk of major adverse cardiotoxic events in ICI-associated myocarditis. Assessment of PD-L1 expression in endomyocardial biopsy specimens may help identify patients at high risk who may benefit from early intervention and closer monitoring.