Team Cancer, Immune Control and Escape, Cordeliers Research Center, UMRS 1138, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France.
University Paris Descartes, Paris, France.
J Transl Med. 2019 Nov 4;17(1):357. doi: 10.1186/s12967-019-2100-3.
The 18-gene tumor inflammation signature (TIS) is a clinical research assay that enriches for clinical benefit to immune checkpoint blockade. We evaluated its ability to predict clinical benefit of immunotherapy in cancer patients treated with PD-1 checkpoint inhibitors in routine clinical care.
The CERTIM cohort is a prospective cohort which includes patients receiving immune checkpoint inhibitors in Cochin University hospital. RNA extracted from 58 archival formalin fixed paraffin embedded tumor blocks (including 38 lung cancers, 5 melanomas, 10 renal carcinomas, 4 urothelial carcinomas and 1 colon carcinoma) was hybridized to a beta version of the NanoString PanCancer IO360™ CodeSet using nCounter technology. Gene expression signatures were correlated with tumor responses (by RECIST criteria) and overall survival. PD-L1 immunostaining on tumor cells was assessed in 37 non-small cell lung cancer (NSCLC) samples and tumor mutational burden (TMB) measured by whole exome sequencing in 19 of these.
TIS scores were significantly associated with complete or partial response to anti-PD-1 treatment in the whole cohort (odds ratio = 2.64, 95% CI [1.4; 6.0], p = 0.008), as well as in the NSCLC population (odds ratio = 3.27, 95% CI [1.2; 11.6], p = 0.03). Patients whose tumor had a high TIS score (upper tertile) showed prolonged overall survival compared to patients whose tumor had lower TIS scores, both in the whole cohort (hazard ratio = 0.37, 95% CI [0.18, 0.76], p = 0.005) and in the NSCLC population (hazard ratio = 0.36, 95% CI [0.14, 0.90], p = 0.02). In the latter, the TIS score was independent from either PD-L1 staining on tumor cells (spearman coefficient 0.2) and TMB (spearman coefficient - 0.2).
These results indicate that validated gene expression assay measuring the level of tumor microenvironment inflammation such as TIS, are accurate and independent predictive biomarkers and can be easily implemented in the clinical practice.
18 基因肿瘤炎症特征（TIS）是一种临床研究检测方法，可增强免疫检查点阻断的临床获益。我们评估了其在常规临床护理中接受 PD-1 检查点抑制剂治疗的癌症患者中预测免疫治疗临床获益的能力。
CERTIM 队列是一项前瞻性队列研究，其中包括在 Cochin 大学医院接受免疫检查点抑制剂治疗的患者。从 58 个存档的福尔马林固定石蜡包埋肿瘤块中提取 RNA（包括 38 个肺癌、5 个黑色素瘤、10 个肾细胞癌、4 个尿路上皮癌和 1 个结肠癌），并用 nCounter 技术对其进行了 Beta 版的 NanoString PanCancer IO360™CodeSet 杂交。基因表达特征与肿瘤反应（根据 RECIST 标准）和总生存相关。在 37 个非小细胞肺癌（NSCLC）样本中评估了肿瘤细胞上的 PD-L1 免疫染色，并在其中的 19 个样本中通过全外显子组测序测量了肿瘤突变负担（TMB）。
TIS 评分与整个队列中抗 PD-1 治疗的完全或部分缓解显著相关（优势比=2.64，95%CI[1.4;6.0]，p=0.008），以及在 NSCLC 人群中（优势比=3.27，95%CI[1.2;11.6]，p=0.03）。与肿瘤 TIS 评分较低的患者相比，肿瘤 TIS 评分较高（上三分位）的患者总生存时间延长，这在整个队列中（风险比=0.37，95%CI[0.18,0.76]，p=0.005）和 NSCLC 人群中（风险比=0.36，95%CI[0.14,0.90]，p=0.02）均如此。在后一种情况下，TIS 评分与肿瘤细胞上的 PD-L1 染色（斯皮尔曼系数 0.2）和 TMB（斯皮尔曼系数-0.2）均无关。
这些结果表明，经过验证的基因表达检测方法，如 TIS，测量肿瘤微环境炎症水平，是准确且独立的预测生物标志物，并且可以在临床实践中轻松实施。
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