PDF(Pubmed)
Abstract：
OBJECTIVE: Small-cell lung cancer (SCLC) is an aggressive disease with a dismal prognosis. The addition of immune checkpoints inhibitors to standard platinum-based chemotherapy in first-line setting achieves a durable benefit only in a patient subgroup. Thus, the identification of predictive biomarkers is an urgent unmet medical need.
METHODS: Tumor samples from naive extensive-stage (ES) SCLC patients receiving atezolizumab plus carboplatin-etoposide were analyzed by gene expression profiling and two 9-color multiplex immunofluorescence panels, to characterize the immune infiltrate and SCLC subtypes. Associations of tissue biomarkers with time-to-treatment failure (TTF), progression-free survival (PFS) and overall survival (OS), were assessed.
RESULTS: 42 patients were included. Higher expression of exhausted CD8-related genes was independently associated with a longer TTF and PFS while increased density of B lymphocytes correlated with longer TTF and OS. Higher percentage of M2-like macrophages close to tumor cells and of CD8+T cells close to CD4+T lymphocytes correlated with increased risk of TF and longer survival, respectively. A lower risk of TF, disease progression and death was associated with a higher density of ASCL1+tumor cells while the expression of POU2F3 correlated with a shorter survival. A composite score combining the expression of exhausted CD8-related genes, B lymphocyte density, ASCL1 tumor expression and quantification of CD163+macrophages close to tumor cells, was able to stratify patients into high-risk and low-risk groups.
CONCLUSIONS: In conclusion, we identified tissue biomarkers and a combined score that can predict a higher benefit from chemoimmunotherapy in ES-SCLC patients.
METHODS: Tumor samples from naive extensive-stage (ES) SCLC patients receiving atezolizumab plus carboplatin-etoposide were analyzed by gene expression profiling and two 9-color multiplex immunofluorescence panels, to characterize the immune infiltrate and SCLC subtypes. Associations of tissue biomarkers with time-to-treatment failure (TTF), progression-free survival (PFS) and overall survival (OS), were assessed.
RESULTS: 42 patients were included. Higher expression of exhausted CD8-related genes was independently associated with a longer TTF and PFS while increased density of B lymphocytes correlated with longer TTF and OS. Higher percentage of M2-like macrophages close to tumor cells and of CD8+T cells close to CD4+T lymphocytes correlated with increased risk of TF and longer survival, respectively. A lower risk of TF, disease progression and death was associated with a higher density of ASCL1+tumor cells while the expression of POU2F3 correlated with a shorter survival. A composite score combining the expression of exhausted CD8-related genes, B lymphocyte density, ASCL1 tumor expression and quantification of CD163+macrophages close to tumor cells, was able to stratify patients into high-risk and low-risk groups.
CONCLUSIONS: In conclusion, we identified tissue biomarkers and a combined score that can predict a higher benefit from chemoimmunotherapy in ES-SCLC patients.
摘要：
目的：小细胞肺癌（SCLC）是一种侵袭性疾病，预后不良。在一线环境中，将免疫检查点抑制剂添加到标准的基于铂的化疗中，仅在患者亚组中实现了持久的益处。因此，预测性生物标志物的识别是一个迫切的未满足的医疗需求。
方法：通过基因表达谱分析和两个9色多重免疫荧光小组分析了接受阿特珠单抗联合卡铂-依托泊苷的幼稚广泛期（ES）SCLC患者的肿瘤样本，表征免疫浸润和SCLC亚型。组织生物标志物与治疗失败时间（TTF）的关联，无进展生存期（PFS）和总生存期（OS），被评估。
结果：纳入42例患者。耗尽的CD8相关基因的较高表达与更长的TTF和PFS独立相关，而B淋巴细胞密度的增加与更长的TTF和OS相关。接近肿瘤细胞的M2样巨噬细胞和接近CD4+T淋巴细胞的CD8+T细胞的百分比较高与TF风险增加和更长的生存期相关。分别。TF的风险较低，疾病进展和死亡与较高密度的ASCL1+肿瘤细胞相关,而POU2F3的表达与较短的生存期相关.结合耗尽的CD8相关基因的表达的综合评分，B淋巴细胞密度,ASCL1肿瘤表达和CD163+巨噬细胞接近肿瘤细胞的定量，能够将患者分为高风险和低风险组。
结论：结论：我们确定了组织生物标志物和联合评分,可以预测ES-SCLC患者接受化学免疫疗法的更高获益.
方法：通过基因表达谱分析和两个9色多重免疫荧光小组分析了接受阿特珠单抗联合卡铂-依托泊苷的幼稚广泛期（ES）SCLC患者的肿瘤样本，表征免疫浸润和SCLC亚型。组织生物标志物与治疗失败时间（TTF）的关联，无进展生存期（PFS）和总生存期（OS），被评估。
结果：纳入42例患者。耗尽的CD8相关基因的较高表达与更长的TTF和PFS独立相关，而B淋巴细胞密度的增加与更长的TTF和OS相关。接近肿瘤细胞的M2样巨噬细胞和接近CD4+T淋巴细胞的CD8+T细胞的百分比较高与TF风险增加和更长的生存期相关。分别。TF的风险较低，疾病进展和死亡与较高密度的ASCL1+肿瘤细胞相关,而POU2F3的表达与较短的生存期相关.结合耗尽的CD8相关基因的表达的综合评分，B淋巴细胞密度,ASCL1肿瘤表达和CD163+巨噬细胞接近肿瘤细胞的定量，能够将患者分为高风险和低风险组。
结论：结论：我们确定了组织生物标志物和联合评分,可以预测ES-SCLC患者接受化学免疫疗法的更高获益.
