Although immune checkpoint blockade (ICB) is currently approved for the treatment of extensive-stage small-cell lung cancer (SCLC) in combination with chemotherapy, relatively few patients have demonstrated durable clinical benefit (DCB) to these therapies. Biomarkers predicting responses are needed. Biopsies from 35 SCLC patients treated with ICB were subjected to transcriptomic analysis; gene signatures were assessed for associations with responses. Twenty-one patients were treated with ICB in the first-line setting in combination with platinum-based chemotherapy; fourteen patients were treated in the second-line setting with ICB alone. DCB after ICB in SCLC in the second-line setting (3 of 14 patients) was associated with statistically higher transcriptomic levels of genes associated with inflammation (p= 0.003), antigen presentation machinery (p= 0.03), interferon responses (p< 0.05), and increased CD8 T cells (p= 0.02). In contrast, these gene signatures were not significantly different in the first-line setting. Our data suggest that responses to ICB in SCLC in the second-line setting can be predicted by the baseline inflammatory state of the tumor; however, this strong association with inflammation was not seen in the first-line setting. We postulate that chemotherapy alters the immune milieu allowing a response to ICB. Other biomarkers will be needed to predict responses in first-line therapy patients.
尽管免疫检查点阻断（ICB）疗法目前已获批准与化疗联合用于广泛期小细胞肺癌（SCLC）的治疗，但相对较少的患者显示出对这些疗法的持久临床获益（DCB）。因此，需要能够预测治疗反应的生物标志物。本研究对35例接受ICB治疗的SCLC患者的活检组织进行了转录组学分析，并评估了基因特征与治疗反应之间的关联。其中，21例患者在一线治疗中接受了ICB联合铂类化疗，14例患者在二线治疗中单独接受了ICB治疗。在二线治疗中，SCLC患者对ICB的持久临床获益（14例患者中有3例）与炎症相关基因（p=0.003）、抗原呈递机制相关基因（p=0.03）、干扰素反应相关基因（p<0.05）转录组水平的统计学显著升高以及CD8 T细胞的增加（p=0.02）相关。相比之下，这些基因特征在一线治疗中并未显示出显著差异。我们的数据表明，二线治疗中SCLC对ICB的反应可以通过肿瘤的基线炎症状态进行预测；然而，这种与炎症的强关联在一线治疗中并未观察到。我们推测，化疗改变了肿瘤的免疫微环境，从而使得患者能够对ICB产生反应。预测一线治疗患者的反应则需要其他生物标志物。
肿瘤(癌症)患者之家