使用闭环系统qRT-PCR测量的PD-L1和PD-L2 mRNA与免疫疗法治疗的非小细胞肺癌的预后有关，并具有较高的阴性预测价值

SCI

16 July 2022

PD-L1 and PD-L2 mRNA measured using closed system qRT-PCR are associated with outcome and high negative predictive value in immunotherapy-treated non-small cell lung cancer

（ J Thorac Oncol  IF:20.121）

• Fernandez AI, Gavrielatou N, McCann L, Shafi S, Moutafi MK, Martinez-Morilla S, Vathiotis IA, Aung TN, Yaghoobi V, Bai Y, Chan YG, Weidler J, Herbst R, Bates M, Rimm DL. PD-L1 and PD-L2 mRNA measured using closed system qRT-PCR are associated with outcome and high negative predictive value in immunotherapy-treated non-small cell lung cancer. J Thorac Oncol. 2022 Jun 25:S1556-0864(22)00311-2. doi: 10.1016/j.jtho.2022.06.007. Epub ahead of print. PMID: 35764237.

Introduction 导言

Immune checkpoint inhibitors (ICIs) have become standard of care in lung cancer management, but only a relatively small percentage of patients treated respond. Current predictive biomarkers, including immunohistochemical (IHC) detection of PD-L1, are insufficient for determining who will respond or, more importantly in the adjuvant setting, who will not respond to ICI therapy. Here, we investigate an alternative method of assessment of PD-L1 to predict non-response.

免疫检查点抑制剂（ICI）已成为肺癌治疗的标准，但只有相对较小比例的治疗患者有反应。目前的预测性生物标志物，包括PD-L1的免疫组化（IHC）检测，不足以确定谁会有反应，或者更重要的是在辅助治疗的情况下，谁会对ICI治疗没有反应。在此，我们研究了一种评估PD-L1的替代方法来预测无反应。

Methods 方法

This study utilizes a research use only quantitative real-time reverse transcription polymerase chain reaction assay on the GeneXpert® (GX) system, to test for the association between 4 target immune genes, CD274 (PD-L1), PDCD1LG2 (PD-L2), CD8A, and IRF1, and response to ICI therapy. Tissues were collected from 122 patients with advanced non-small cell lung cancer prior to ICI therapy in a retrospective cohort, macro-dissected, and analyzed using the GX.

本研究利用GeneXpert® (GX)系统的定量实时反转录聚合酶链式反应检测4个目标免疫基因CD274 (PD-L1)、PDCD1LG2 (PD-L2)、CD8A和IRF1与ICI治疗反应之间的关系。在一个回顾性队列中，收集了122名晚期非小细胞肺癌患者在接受ICI治疗前完全切除的组织，并使用GX进行分析。

Results 结果

Both high PD-L1 and PD-L2 mRNA expression levels were associated with improved long-term benefit at 24 months (p=0.047 for both PD-L1 and PD-L2) and overall survival (PD-L1, p= 0.048; PD-L2 p= 0.049). Both PD-L1 and PD-L2 mRNA levels were higher in patients with KRAS mutations. Most importantly, low PD-L1 mRNA showed a high negative predictive value of 0.92 for absence of long-term benefit.

高的PD-L1和PD-L2 mRNA表达水平都与24个月的长期获益（PD-L1和PD-L2的p=0.047）和总生存率（PD-L1，p=0.048；PD-L2 p=0.049）的改善有关。在KRAS突变的患者中，PD-L1和PD-L2的mRNA水平都比较高。最重要的是，低的PD-L1 mRNA显示出很高的阴性预测值，即0.92，说明没有长期受益。

Conclusions 结论

With further validation this assay in low stage patients, assessment of PD-L1 mRNA rather than protein, could be a method to determine which low stage patients should not be treated with ICIs in the adjuvant setting. This approach may also be a useful objective method for selecting patients for treatment in the advanced setting.

随着进一步的验证，这种对早期患者的检测，对PD-L1 mRNA而不是蛋白质的评估，可以成为确定哪些低期患者不应该在辅助治疗中使用ICIs的方法。这种方法也可能是一种有用的客观方法，用于选择晚期患者的治疗。

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