PDF(Pubmed)
Abstract：
UNASSIGNED: Immunotherapy has shown intracranial efficacy in non-small cell lung cancer (NSCLC) patients with brain metastases. However, predictive biomarkers for intracranial response to immunotherapy are lacking. This post-hoc analysis aimed to explore the potential of immunological cytokines in cerebrospinal fluid (CSF) to predict intracranial tumor response to immunotherapy in patients with brain metastases.
UNASSIGNED: Treatment-naive NSCLC patients with brain metastases who received camrelizumab plus chemotherapy were enrolled. Paired plasma and CSF samples were prospectively collected at baseline and the first treatment assessment. All samples were analyzed for 92 immuno-oncology cytokines using Olink\'s panels.
UNASSIGNED: A total of 28 patients were included in this analysis. At baseline, most immunological cytokines were significantly lower in CSF than in plasma, whereas a subset comprising CD83, PTN, TNFRSF21, TWEAK, ICOSLG, DCN, IL-8, and MCP-1, was increased in CSF. Baseline CSF levels of LAMP3 were significantly higher in patients with intracranial tumor response, while the levels of CXCL10, IL-12, CXCL11, IL-18, TIE2, HGF, and PDCD1 were significantly lower. Furthermore, the CXCL10, CXCL11, TIE2, PDCD1, IL-18, HGF, and LAMP3 in CSF were also significantly associated with intracranial progression-free survival for immunotherapy. The identified cytokines in CSF were decreased at the first treatment evaluation in patients with intracranial tumor response. The logistic CSF immuno-cytokine model yielded an AUC of 0.91, as compared to PD-L1 expression (AUC of 0.72).
UNASSIGNED: Immunological cytokines in CSF could predict intracranial tumor response to immunotherapy in NSCLC patients with brain metastases, and the findings warrant validation in a larger prospective cohort study.
UNASSIGNED: ClinicalTrials.gov identifier: NCT04211090.
UNASSIGNED: Treatment-naive NSCLC patients with brain metastases who received camrelizumab plus chemotherapy were enrolled. Paired plasma and CSF samples were prospectively collected at baseline and the first treatment assessment. All samples were analyzed for 92 immuno-oncology cytokines using Olink\'s panels.
UNASSIGNED: A total of 28 patients were included in this analysis. At baseline, most immunological cytokines were significantly lower in CSF than in plasma, whereas a subset comprising CD83, PTN, TNFRSF21, TWEAK, ICOSLG, DCN, IL-8, and MCP-1, was increased in CSF. Baseline CSF levels of LAMP3 were significantly higher in patients with intracranial tumor response, while the levels of CXCL10, IL-12, CXCL11, IL-18, TIE2, HGF, and PDCD1 were significantly lower. Furthermore, the CXCL10, CXCL11, TIE2, PDCD1, IL-18, HGF, and LAMP3 in CSF were also significantly associated with intracranial progression-free survival for immunotherapy. The identified cytokines in CSF were decreased at the first treatment evaluation in patients with intracranial tumor response. The logistic CSF immuno-cytokine model yielded an AUC of 0.91, as compared to PD-L1 expression (AUC of 0.72).
UNASSIGNED: Immunological cytokines in CSF could predict intracranial tumor response to immunotherapy in NSCLC patients with brain metastases, and the findings warrant validation in a larger prospective cohort study.
UNASSIGNED: ClinicalTrials.gov identifier: NCT04211090.
摘要：
■免疫治疗已显示出脑转移非小细胞肺癌（NSCLC）患者的颅内疗效。然而,缺乏免疫疗法颅内反应的预测性生物标志物.这项事后分析旨在探索脑脊液（CSF）中免疫细胞因子预测脑转移患者颅内肿瘤对免疫治疗反应的潜力。
■纳入接受卡姆瑞珠单抗联合化疗的未治疗脑转移NSCLC患者。在基线和第一次治疗评估时前瞻性地收集配对的血浆和CSF样品。使用Olink小组分析所有样品的92种免疫肿瘤学细胞因子。
■本分析共纳入28例患者。在基线,大多数免疫细胞因子在CSF中显著低于血浆,而包含CD83、PTN、TNFRSF21,TWEAK,ICOSLG，DCN,IL-8和MCP-1在CSF中增加。有颅内肿瘤反应的患者的基线CSF水平显著较高，而CXCL10，IL-12，CXCL11，IL-18，TIE2，HGF的水平，和PDCD1显著降低。此外，CXCL10，CXCL11，TIE2，PDCD1，IL-18，HGF，CSF中的LAMP3也与免疫治疗的颅内无进展生存期显著相关.在具有颅内肿瘤反应的患者中，首次治疗评估时，CSF中鉴定的细胞因子降低。与PD-L1表达(AUC为0.72)相比,逻辑CSF免疫细胞因子模型产生0.91的AUC。
■CSF中的免疫细胞因子可以预测伴有脑转移的NSCLC患者对免疫疗法的颅内肿瘤反应，这些发现值得在更大的前瞻性队列研究中验证。
■ClinicalTrials.gov标识符：NCT04211090。
■纳入接受卡姆瑞珠单抗联合化疗的未治疗脑转移NSCLC患者。在基线和第一次治疗评估时前瞻性地收集配对的血浆和CSF样品。使用Olink小组分析所有样品的92种免疫肿瘤学细胞因子。
■本分析共纳入28例患者。在基线,大多数免疫细胞因子在CSF中显著低于血浆,而包含CD83、PTN、TNFRSF21,TWEAK,ICOSLG，DCN,IL-8和MCP-1在CSF中增加。有颅内肿瘤反应的患者的基线CSF水平显著较高，而CXCL10，IL-12，CXCL11，IL-18，TIE2，HGF的水平，和PDCD1显著降低。此外，CXCL10，CXCL11，TIE2，PDCD1，IL-18，HGF，CSF中的LAMP3也与免疫治疗的颅内无进展生存期显著相关.在具有颅内肿瘤反应的患者中，首次治疗评估时，CSF中鉴定的细胞因子降低。与PD-L1表达(AUC为0.72)相比,逻辑CSF免疫细胞因子模型产生0.91的AUC。
■CSF中的免疫细胞因子可以预测伴有脑转移的NSCLC患者对免疫疗法的颅内肿瘤反应，这些发现值得在更大的前瞻性队列研究中验证。
■ClinicalTrials.gov标识符：NCT04211090。
