Multidimensional Analysis of B7 Homolog 3 RNA Expression in Small Cell Lung Cancer Molecular Subtypes

作者：Gay CM, Owonikoko TK, Byers LA, Choudhury NJ, Ahmed S, Cain Z, Qian X, Brentnall M, Heeke S, Poi M, Wu S, Rudin CM · 发表于：Clinical cancer research : an official journal of the American Association for Cancer Research · 年份：2025 · DOI：10.1158/1078-0432.ccr-24-3981 · 被引用次数：22 · 研究领域：Small Cell Lung Carcinoma、B7 Antigens、Lung Neoplasms、Biomarkers, Tumor、Humans、Male、Female、B7-H1 Antigen、Gene Expression Regulation, Neoplastic、Middle Aged、Aged、Mutation

PURPOSE: B7 homolog 3 (B7-H3) is a promising target for antibody-drug conjugates, with ifinatamab deruxtecan demonstrating an objective response rate of 54.8% in previously treated extensive-stage small cell lung cancer (SCLC). This analysis aimed to characterize B7-H3 RNA expression with reference to SCLC molecular subtypes (SCLC-A, SCLC-N, SCLC-P, and SCLC-I) and immune-related parameters. EXPERIMENTAL DESIGN: Tumor RNA expression and mutational burden for 1,721 patients with SCLC were derived from a real-world database (Caris Life Sciences). A predominant molecular subtype was assigned based on RNA expression using a gene-ratio classifier. PD-L1 expression was assessed by IHC (antibody 22C3; positive cutoff: tumor proportion score ≥1%). RESULTS: The predominant molecular subtype was SCLC-A in 848 (49.3%), SCLC-N in 202 (11.7%), SCLC-P in 142 (8.3%), SCLC-I in 291 (16.9%), and equivocal in 238 (13.8%) samples. B7-H3 expression was high and consistent among subtypes (q > 0.05), whereas DLL3 and SEZ6 expression each differed significantly (both q < 0.0001). PD-L1 positivity was similar across B7-H3 expression quartiles (range, 39.2%-46.5%). Median (95% confidence interval) B7-H3 expression was comparable between patients with and without prior immunotherapy [18.7 (16.5-21.2) and 17.3 (16.4-18.1) transcripts per million, respectively]. B7-H3 was not correlated with a T-cell signature but showed a strong correlation with HAVCR2/TIM3, CD86, PDCD1LG2/PD-L2, and M2 macrophages. ...