小细胞肺癌二线疗法中检查点阻断剂反应的预测信号不能预测一线患者的反应

Cancers Pub Date : 2024-08-08 DOI:10.3390/cancers16162795
Jeffrey C. Thompson, Caitlin M Tilsed, Christiana W. Davis, Aasha Gupta, Bihui Melidosian, Chifei Sun, Michael E Kallen, Cynthia Timmers, Corey J. Langer, Steven M. Albelda
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引用次数: 0

摘要

尽管免疫检查点阻断疗法(ICB)目前已被批准与化疗联合用于广泛期小细胞肺癌(SCLC)的治疗,但相对较少的患者能从这些疗法中获得持久的临床获益(DCB)。因此需要生物标志物来预测反应。对35名接受ICB治疗的SCLC患者的活检组织进行了转录组分析;评估了基因特征与反应的关联。21名患者在一线治疗中接受了ICB与铂类化疗的联合治疗;14名患者在二线治疗中接受了ICB单药治疗。二线治疗 SCLC 的 ICB 后 DCB(14 例患者中的 3 例)与炎症(p = 0.003)、抗原递呈机制(p = 0.03)、干扰素反应(p < 0.05)和 CD8 T 细胞增加(p = 0.02)相关基因的转录组水平较高有关。相比之下,这些基因特征在一线治疗中没有明显差异。我们的数据表明,肿瘤的基线炎症状态可预测二线治疗 SCLC 对 ICB 的反应;然而,这种与炎症的密切关系在一线治疗中并不存在。我们推测化疗改变了免疫环境,从而对 ICB 产生了反应。预测一线治疗患者的反应还需要其他生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Predictive Signatures for Responses to Checkpoint Blockade in Small-Cell Lung Cancer in Second-Line Therapy Do Not Predict Responses in First-Line Patients
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.
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