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

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.

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.

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.

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.