Identification of inflamed-phenotype of small cell lung cancer leading to the efficacy of anti-PD-L1 antibody and chemotherapy
Identification of inflamed-phenotype of small cell lung cancer leading to the efficacy of anti-PD-L1 antibody and chemotherapy
复制标题
鉴定小细胞肺癌炎症表型，提高抗 PD-L1 抗体和化疗的疗效
DOI：
10.1016/j.lungcan.2023.107183
复制
发表时间：
2023
期刊：
影响因子：
5.3
通讯作者：
et al.
中科院分区：
文献类型：
--
作者：
Shirasawa Masayuki;Yoshida Tatsuya;Shiraishi Kouya;et al.
背景铂依托泊苷加抗程序性细胞死亡配体-1 （PD-L1）抗体治疗是广泛期小细胞肺癌（ES-SCLC）的标准治疗方案。然而，与SCLC联合治疗疗效相关的患者特征尚不清楚。方法回顾性分析阿特唑单抗联合卡铂和依托泊苷（ACE）治疗的术后有限期(LS)-SCLC和ES-SCLC患者。在LS-SCLC队列中，研究了基于转录组学数据的SCLC亚型与病理结果（包括cd8阳性肿瘤浸润淋巴细胞（TIL）状态）之间的关系。在ES-SCLC队列中评估了ACE治疗的疗效、病理亚型和TIL状态之间的关系。结果根据转录组学数据，将LS-SCLC队列（N = 48）分为4种SCLC亚型（ASCL1 + NEUROD1 [SCLC- a + N, N = 17]、POU2F3 [SCLC- p, N = 15]、YAP1 [SCLC- y, N = 10]和炎症[SCLC- i， N = 6]）。SCLC-I在转录亚型中表现出丰富的免疫相关通路，最高的免疫评分（CD8A表达和t细胞炎症基因表达谱）和上皮-间质转化（EMT）。免疫组化染色（IHC）显示SCLC-I在转录亚型中cd8阳性TILs密度最高。在ES-SCLC队列中，ACE治疗的疗效没有因病理亚型而异。tilhigh患者的无进展生存期（PFS）明显长于tillow患者（PFS: 7.3个月vs. 4.0个月，p < 0.001）。结论基于转录组学数据，具有高密度TILs的肿瘤可从ACE治疗中获益，这是最具免疫原性的SCLC亚型（SCLC- i）。
BackgroundPlatinum etoposide plus anti-programmed cell death ligand-1 (PD-L1) antibody therapy is the standard of care for extensive-stage small cell lung cancer (ES-SCLC). However, patient characteristics associated with the efficacy of the combination therapy in SCLC are unclear.MethodsWe retrospectively reviewed post-surgical limited-stage (LS)-SCLC and ES-SCLC patients treated with atezolizumab plus carboplatin and etoposide (ACE). The association between SCLC subtypes based on transcriptomic data and pathological findings, including CD8-positive tumor-infiltrating lymphocyte (TIL) status, was investigated in the LS-SCLC cohort. The association between the efficacy of ACE therapy, pathological subtypes, and TIL status was evaluated in the ES-SCLC cohort.ResultsThe LS-SCLC cohort (N = 48) was classified into four SCLC subtypes (ASCL1 + NEUROD1 [SCLC-A + N, N = 17], POU2F3 [SCLC-P, N = 15], YAP1 [SCLC-Y, N = 10], and inflamed [SCLC-I, N = 6]) based on transcriptomic data. SCLC-I showed enriched immune-related pathways, the highest immune score (CD8A expression and T-cell–inflamed gene expression profiles), and epithelial–mesenchymal transition (EMT), in transcriptional subtypes. Immunohistochemical staining (IHC) showed that SCLC-I had the highest density of CD8-positive TILs in transcriptional subtypes. In the ES-SCLC cohort, the efficacy of ACE therapy did not differ according to pathological subtypes. The progression-free survival (PFS) of TILHighpatients was significantly longer than that of TILLowpatients (PFS: 7.3 months vs. 4.0 months, p < 0.001).ConclusionTumors with a high density of TILs, which represent the most immunogenic SCLC subtype (SCLC-I), based on transcriptomic data could benefit from ACE therapy.