Exploring the Expression of CD73 in Lung Adenocarcinoma with EGFR Genomic Alterations

Background/Objectives: Immune checkpoint inhibitors (ICIs) benefit some lung cancer patients, but their efficacy is limited in advanced lung adenocarcinoma (LUAD) with EGFR mutations (EGFRm), largely due to a non-immunogenic tumour microenvironment (TME). Furthermore, EGFRm LUAD patients often experience increased toxicity with ICIs. CD73, an ectonucleotidase involved in adenosine production, promotes tumour immune evasion and could represent a novel therapeutic target. This study investigates CD73 expression in LUAD with EGFR alterations and its clinico-pathological correlations. Methods: CD73 expression in tumour (CD73(TC)) and stromal (CD73(SC)) cells was assessed in 76 treatment-naive LUAD patients using immunohistochemistry (IHC) (D7F9A clone) alongside IHC PD-L1 (22C3 clone). EGFR alterations were identified by molecular sequencing and FISH. Event-free survival (EFS) was analysed based on CD73(TC) expression. Results: CD73(TC) expression was observed in 66% of cases, with high expression (Tumour Proportion Score > 50%) correlating with improved EFS (p = 0.045). CD73(TC) and PD-L1 expression were not significantly correlated (p = 0.44), although a weak inverse trend was observed. CD73(SC) expression was detected in 18% of cases, predominantly in early-stage (p = 0.037), PD-L1-negative (p = 0.030), and non-EGFR-amplified (p = 0.0018) tumours. No significant associations were found with disease stage, histological subtype, EGFR mutation type, and amplification. Conclusions: CD73 expression in EGFRm LUAD is heterogeneous and associated with diverse TME profiles. These findings support the potential of CD73 as a predictive biomarker and therapeutic target, highlighting its clinical relevance in EGFRm LUAD.