PD-L1 Expression in Systemic Immune Cell Populations as a Potential Predictive Biomarker of Responses to PD-L1/PD-1 Blockade Therapy in Lung Cancer
PD-L1 Expression in Systemic Immune Cell Populations as a Potential Predictive Biomarker of Responses to PD-L1/PD-1 Blockade Therapy in Lung Cancer
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DOI：
10.3390/ijms20071631
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发表时间：
2019-04-02
影响因子：
5.6
通讯作者：
Kochan, Grazyna
中科院分区：
文献类型：
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作者：
Bocanegra, Ana;Fernandez-Hinojal, Gonzalo;Kochan, Grazyna
PD-L1肿瘤表达是PD-L1/PD-1阻断抗癌治疗中广泛用于患者分层的生物标志物，尤其是对肺癌患者。然而，这一标记的可靠性仍在争论中。此外，PD-L1在多种免疫细胞类型中广泛表达，而系统性PD-L1(+)细胞与免疫检查点阻断反应的相关性知之甚少。我们提出了两个非小细胞肺癌(NSCLC)和PD-L1阴性肿瘤患者使用阿替唑单抗治疗的临床病例，这些患者表现出客观的缓解或进展。这些患者在系统免疫细胞中PD-L1的表达分布有很大差异。基于这些结果，对32例接受PD-L1/PD-1阻断治疗的NSCLC患者进行了探索性研究，以比较PD-L1的表达谱及其与临床结果的关系。目的应答者和无应答者的PD-L1(+)、CD11b(+)髓系细胞百分率有显著差异。在免疫治疗开始前PD-L1(+)CD11b(+)细胞百分比超过30%的患者的应答率为50%，结合记忆CD4T细胞图谱的应答率为70%。这些发现表明，即使活检评分为PD-L1阴性，对系统性PD-L1(+)髓系细胞亚群的量化也可以为患者分层提供一个简单的生物标记物。
PD-L1 tumor expression is a widely used biomarker for patient stratification in PD-L1/PD-1 blockade anticancer therapies, particularly for lung cancer. However, the reliability of this marker is still under debate. Moreover, PD-L1 is widely expressed by many immune cell types, and little is known on the relevance of systemic PD-L1(+) cells for responses to immune checkpoint blockade. We present two clinical cases of patients with non-small cell lung cancer (NSCLC) and PD-L1-negative tumors treated with atezolizumab that showed either objective responses or progression. These patients showed major differences in the distribution of PD-L1 expression within systemic immune cells. Based on these results, an exploratory study was carried out with 32 cases of NSCLC patients undergoing PD-L1/PD-1 blockade therapies, to compare PD-L1 expression profiles and their relationships with clinical outcomes. Significant differences in the percentage of PD-L1(+) CD11b(+) myeloid cell populations were found between objective responders and non-responders. Patients with percentages of PD-L1(+) CD11b(+) cells above 30% before the start of immunotherapy showed response rates of 50%, and 70% when combined with memory CD4 T cell profiling. These findings indicate that quantification of systemic PD-L1(+) myeloid cell subsets could provide a simple biomarker for patient stratification, even if biopsies are scored as PD-L1 null.