Comprehensive genomic and spatial immune infiltration analysis of survival outliers in extensive-stage small cell lung cancer receiving first-line chemoimmunotherapy

作者：Yuxin Jiang, Jingyuan Xie, Qinpei Cheng, Zijing Cai, Ke Xu, Wanjun Lu, Fufeng Wang, Xiaoying Wu, Yong Song, Tangfeng Lv, Ping Zhan · 发表于：International Immunopharmacology · 年份：2024 · DOI：10.1016/j.intimp.2024.112901 · 被引用次数：9 · 研究领域：Lung Cancer Research Studies、Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis

Background A minority of patients with extensive-stage small cell lung cancer (ES-SCLC) exhibit prolonged survival following first-line chemoimmunotherapy, which warrants the use of reliable biomarkers. Here, we investigated the disparities in genomics and immune cell spatial distribution between long- and short-term survival of patients with ES-SCLC. Methods We retrospectively recruited 11 long-term (>2 years) and 13 short-term (<9 months) ES-SCLC survivors receiving first-line chemoimmunotherapy. The samples were processed using targeted next-generation sequencing (tNGS), programmed death ligand-1 staining, multiplex immunohistochemical staining for immune cells (mIHC), tumor mutation burden (TMB), and chromosomal instability score measurements. The expression of putative genes in SCLC at the bulk and single-cell RNA-sequencing levels, as well as the role of putative genes in pan-cancer immunotherapy cohorts, were analyzed. Results At the genomic level, a greater proportion of the smoking signature and higher TMB (>3.1) were associated with favorable survival. At the single-gene and pathway levels, tNGS revealed that MCL1 and STMN1 amplification and alterations in the apoptosis pathway were more common in short-term survivors, whereas alterations in the DLL3 , KMT2B , HGF , EPHA3 , ADGRB3 , lysine deprivation, and HGF-cMET pathways were observed more frequently in long-term survivors. mIHC analysis of immune cells with different spatial distributions revealed that long-term...