Association of tumor CD73 expression with clinical outcomes in small cell lung cancer treated with first-line chemo-immunotherapy

BACKGROUND: Small cell lung cancer (SCLC) is a highly aggressive malignancy with limited therapeutic options. Immune checkpoint inhibitors (ICIs) modestly improve outcomes, but predictive biomarkers are lacking. CD73, an ecto-5'-nucleotidase, generates immunosuppressive adenosine and may attenuate ICI efficacy. METHODS: We conducted a single-center, retrospective study of 36 SCLC patients receiving first-line platinum-based chemo-immunotherapy. Tumor CD73 expression was assessed by immunohistochemistry and dichotomized as negative (H-score = 0) or positive (H-score ≥ 1). Molecular subtypes were determined based on dominant transcription factor expression (ASCL1, NEUROD1, POU2F3, YAP1). Associations between CD73 expression, progression-free survival (PFS), overall survival (OS), and transcriptional subtypes were analyzed. Public RNA-sequencing data (GSE69091) were used to contextualize immune-related gene expression patterns. RESULTS: CD73 was positive in 75% of tumors. CD73-positive patients exhibited significantly shorter median PFS compared with CD73-negative patients (4.0 vs. 7.9 months; p = 0.048) and a trend toward reduced OS (8.5 vs. 29.1 months; p = 0.249). CD73 expression was not significantly associated with molecular subtypes. Public dataset analysis revealed CD73-high tumors with elevated T cell and immunosuppressive gene expression, but no OS difference in an ICI-naïve cohort, suggesting that CD73's impact is treatment-specific. CONCLUSIONS: Tumor CD73 expression is associated with inferior PFS in SCLC patients receiving chemo-immunotherapy and may serve as a predictive biomarker for ICI efficacy. Immunohistochemistry-based assessment of CD73 might facilitate treatment stratification, and prospective studies evaluating CD73-targeted therapies in combination with ICIs are warranted.