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不可切除胰腺癌中可溶性程序性死亡配体 1 及其在化疗期间动态变化的预后意义。

Prognostic implications of soluble programmed death-ligand 1 and its dynamics during chemotherapy in unresectable pancreatic cancer.

机构信息

Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.

Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.

出版信息

Sci Rep. 2019 Jul 31;9(1):11131. doi: 10.1038/s41598-019-47330-1.

Abstract

In pancreatic cancer, acquiring a sufficient amount of tumor tissue is an obstacle. The soluble form of PD-L1 (sPD-L1) may have immunosuppressive activity. Here, we evaluated the prognostic implications of sPD-L1 in unresectable pancreatic cancer. We prospectively enrolled 60 patients treated with first-line FOLFIRINOX chemotherapy. We collected blood samples at diagnosis, first response assessment and disease progression. Serum sPD-L1 levels were measured using enzyme-linked immunosorbent assays. The median sPD-L1 level was 1.7 ng/mL (range, 0.4-5.7 ng/mL). Patients with low sPD-L1 level (<4.6 ng/mL) at diagnosis showed better overall survival (OS) than those with high sPD-L1 level (P = 0.015). Multivariate analysis identified sPD-L1 and the neutrophil-to-lymphocyte ratio as independent prognostic factors for OS. During chemotherapy, more patients achieved complete response (CR)/partial response (PR) as their best response when sPD-L1 was decreased at the first response assessment (P = 0.038). In the patients who achieved CR/PR as their best response, sPD-L1 was significantly higher at the time of disease progression than at the first response assessment (P = 0.025). In conclusion, the sPD-L1 level at diagnosis exhibits a prognostic value in pancreatic cancer. Furthermore, sPD-L1 dynamics correlate with disease course and could be used to understand various changes in the tumor microenvironment during chemotherapy.

摘要

在胰腺癌中,获得足够量的肿瘤组织是一个障碍。PD-L1 的可溶性形式(sPD-L1)可能具有免疫抑制活性。在这里,我们评估了 sPD-L1 在不可切除的胰腺癌中的预后意义。我们前瞻性地招募了 60 名接受一线 FOLFIRINOX 化疗的患者。我们在诊断时、首次反应评估时和疾病进展时采集了血液样本。使用酶联免疫吸附试验测量血清 sPD-L1 水平。sPD-L1 水平的中位数为 1.7ng/mL(范围,0.4-5.7ng/mL)。在诊断时 sPD-L1 水平较低(<4.6ng/mL)的患者总生存期(OS)优于 sPD-L1 水平较高的患者(P=0.015)。多变量分析确定 sPD-L1 和中性粒细胞与淋巴细胞比值是 OS 的独立预后因素。在化疗期间,当首次反应评估时 sPD-L1 下降时,更多的患者达到完全缓解(CR)/部分缓解(PR)作为最佳反应(P=0.038)。在达到 CR/PR 作为最佳反应的患者中,sPD-L1 在疾病进展时明显高于首次反应评估时(P=0.025)。总之,诊断时的 sPD-L1 水平在胰腺癌中具有预后价值。此外,sPD-L1 动力学与疾病过程相关,可以用来了解化疗过程中肿瘤微环境的各种变化。

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