Exploring the predictive potential of programmed death ligand 1 expression in healthy organs and lymph nodes as...

Immune checkpoint inhibitors (ICIs) can elicit anticancer immune responses, but predictive biomarkers are needed. We measured programmed death ligand 1 (PD-L1) expression in organs and lymph nodes using ¹⁸F-BMS-986192 positron emission tomography (PET)-imaging and looked for correlations with response and immune-related adverse events.

Four ¹⁸F-BMS-986192 PET studies in patients with melanoma, lung, pancreatic and oral cancer, receiving ICI treatment, were combined. Imaging data (organ standardized uptake value (SUV)_mean, lymph node SUV_max) and clinical data (response to treatment and incidence of immune-related adverse events) were extracted.

Baseline PD-L1 uptake in the spleen was on average higher in non-responding patients than in responders (spleen SUV_mean 16.1±4.4 vs 12.5±3.4, p=0.02). This effect was strongest in lung cancer, and not observed in oral cancer. In the oral cancer cohort, benign tumor-draining lymph nodes (TDLNs) had higher PD-L1 uptake (SUV_max 3.3 IQR 2.5-3.9) compared with non-TDLNs (SUV_max 1.8, IQR 1.4-2.8 p=0.04). Furthermore, in the same cohort non-responders showed an increase in PD-L1 uptake in benign TDLNs on-treatment with ICIs (+15%), while for responders the PD-L1 uptake decreased (-11%). PD-L1 uptake did not predict immune-related adverse events, though elevated thyroid uptake on-treatment correlated with pre-existing thyroid disease or toxicity.

PD-L1 PET uptake in the spleen is a potential negative predictor of response to ICIs. On-treatment with ICIs, PD-L1 uptake in benign TDLNs increases in non-responders, while it decreases in responders, potentially indicating a mechanism for resistance to ICIs in patients with oral cancer.