Contribution of PD-L1-expressing tumor and immune cells to the Combined Positive Score (CPS) using PD-L1 IHC 22C3 pharmDx

PD-L1 IHC 22C3 pharmDx (SK006) is currently FDA-approved for use with pembrolizumab (KEYTRUDA) for non-small cell lung cancer, esophageal squamous cell cancer, cervical cancer, head and neck squamous cell carcinoma (HNSCC), triple-negative breast cancer (TNBC), and gastric and gastroesophageal junction (GC/GEJ) adenocarcinoma. This study evaluates the contribution of PD-L1 staining tumor cells (TCs) and mononuclear inflammatory cells (MICs) when determining the Combined Positive Score (CPS) with SK006. We retrospectively analyzed TNBC, urothelial carcinoma (UC), HNSCC, esophageal cancer (EC), and GC/GEJ specimens. Specimens were stained and scored using CPS (PD-L1 staining TCs and MICs) and Tumor Proportion Score (TPS; PD-L1 staining TCs only). We then determined a specimen’s calculated immune cell density (CID), and TC/MIC PD-L1 expression ratio. Analysis revealed PD-L1-expressing TCs and MICs were both present in 36% of all specimens. PD-L1-expressing TCs contributed significantly more than MICs in specimens above CPS ≥ 10 and CPS ≥ 20 cutoffs. Collectively, these results demonstrate that while the CPS for some tumor types is driven by PD-L1-expressing MICs, PD-L1-expressing TCs may drive the CPS above a cutoff for other tumor types. As such, both TCs and MICs remain important contributors to the CPS. These findings highlight CPS as a comprehensive scoring algorithm when using SK006.