Missing prognostic value of soluble PD-1, PD-L1 and PD-L2 in lung cancer patients undergoing chemotherapy - A CEPAC-TDM biomarker substudy.

Q3 Biochemistry, Genetics and Molecular Biology Tumor Biology Pub Date : 2024-01-01 DOI:10.3233/TUB-230015
Kimberly Geiger, Markus Joerger, Max Roessler, Karina Hettwer, Christoph Ritter, Kirsten Simon, Steffen Uhlig, Stefan Holdenrieder
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Abstract

Background: Programmed cell death receptors and ligands in cancer tissue samples are established companion diagnostics for immune checkpoint inhibitor (ICI) therapies.

Objective: To investigate the relevance of soluble PD-1, PD-L1 and PD-L2 for estimating therapy response and prognosis in non-small cell lung cancer patients (NSCLC) undergoing platin-based combination chemotherapies.

Methods: In a biomarker substudy of a prospective, multicentric clinical trial (CEPAC-TDM) on advanced NSCLC patients, soluble PD-1, PD-L1 and PD-L2 were assessed in serial serum samples by highly sensitive enzyme-linked immunosorbent assays and correlated with radiological response after two cycles of chemotherapy and with overall survival (OS).

Results: Among 243 NSCLC patients, 185 achieved response (partial remission and stable disease) and 58 non-response (progression). The distribution of PD-1, PD-L1 and PD-L2 at baseline (C1), prior to staging (C3) and the relative changes (C3/C1) greatly overlapped between the patient groups with response and non-response, thus hindering the discrimination between the two groups. None of the PD markers had prognostic value regarding OS.

Conclusions: Neither soluble PD-1, PD-L1 nor PD-L2 did provide clinical utility for predicting response to chemotherapy and prognosis. Studies on the relevance of PD markers in ICI therapies are warranted.

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可溶性 PD-1、PD-L1 和 PD-L2 在接受化疗的肺癌患者中缺失的预后价值--CEPAC-TDM 生物标志物子研究。
背景:癌症组织样本中的程序性细胞死亡受体和配体是免疫检查点抑制剂(ICI)疗法的成熟辅助诊断方法:目的:研究可溶性PD-1、PD-L1和PD-L2与估计接受铂类联合化疗的非小细胞肺癌(NSCLC)患者的治疗反应和预后的相关性:在一项针对晚期NSCLC患者的前瞻性多中心临床试验(CEPAC-TDM)的生物标志物子研究中,通过高灵敏度的酶联免疫吸附试验对连续血清样本中的可溶性PD-1、PD-L1和PD-L2进行了评估,并将其与两个化疗周期后的放射学反应和总生存期(OS)相关联:结果:在243例NSCLC患者中,185例获得应答(部分缓解和病情稳定),58例无应答(病情进展)。PD-1、PD-L1和PD-L2在基线(C1)、分期前(C3)和相对变化(C3/C1)的分布在有反应和无反应患者组之间有很大重叠,因此阻碍了两组之间的区分。没有一个PD标记物对OS有预后价值:结论:可溶性PD-1、PD-L1和PD-L2都不能用于预测化疗反应和预后。有必要对PD标记物在ICI疗法中的相关性进行研究。
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来源期刊
Tumor Biology
Tumor Biology 医学-肿瘤学
CiteScore
5.40
自引率
0.00%
发文量
18
审稿时长
1 months
期刊介绍: Tumor Biology is a peer reviewed, international journal providing an open access forum for experimental and clinical cancer research. Tumor Biology covers all aspects of tumor markers, molecular biomarkers, tumor targeting, and mechanisms of tumor development and progression. Specific topics of interest include, but are not limited to: Pathway analyses, Non-coding RNAs, Circulating tumor cells, Liquid biopsies, Exosomes, Epigenetics, Cancer stem cells, Tumor immunology and immunotherapy, Tumor microenvironment, Targeted therapies, Therapy resistance Cancer genetics, Cancer risk screening. Studies in other areas of basic, clinical and translational cancer research are also considered in order to promote connections and discoveries across different disciplines. The journal publishes original articles, reviews, commentaries and guidelines on tumor marker use. All submissions are subject to rigorous peer review and are selected on the basis of whether the research is sound and deserves publication. Tumor Biology is the Official Journal of the International Society of Oncology and BioMarkers (ISOBM).
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