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

BACKGROUND/OBJECTIVES: Immune checkpoint inhibitors (ICIs) benefit some lung cancer patients, but their efficacy is limited in advanced lung adenocarcinoma (LUAD) with mutations (), largely due to a non-immunogenic tumour microenvironment (TME). Furthermore, 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 alterations and its clinico-pathological correlations.

METHODS

CD73 expression in tumour (CD73) and stromal (CD73) cells was assessed in 76 treatment-naive LUAD patients using immunohistochemistry (IHC) (D7F9A clone) alongside IHC PD-L1 (22C3 clone). alterations were identified by molecular sequencing and FISH. Event-free survival (EFS) was analysed based on CD73 expression.

RESULTS

CD73 expression was observed in 66% of cases, with high expression (Tumour Proportion Score > 50%) correlating with improved EFS ( = 0.045). CD73 and PD-L1 expression were not significantly correlated ( = 0.44), although a weak inverse trend was observed. CD73 expression was detected in 18% of cases, predominantly in early-stage ( = 0.037), PD-L1-negative ( = 0.030), and non--amplified ( = 0.0018) tumours. No significant associations were found with disease stage, histological subtype, mutation type, and amplification.

CONCLUSIONS

CD73 expression in 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 LUAD.