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循环单核细胞髓系来源的抑制性样细胞水平高与晚期非小细胞肺癌对免疫检查点抑制剂的原发性耐药相关：一项探索性分析。

High Levels of Circulating Monocytic Myeloid-Derived Suppressive-Like Cells Are Associated With the Primary Resistance to Immune Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer: An Exploratory Analysis.

机构信息

Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, Ancona, Italy.

Unit of Biostatistics and Clinical Trials, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.

出版信息

Front Immunol. 2022 Apr 13;13:866561. doi: 10.3389/fimmu.2022.866561. eCollection 2022.

DOI:10.3389/fimmu.2022.866561
PMID:35493483
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9043492/
Abstract

BACKGROUND

Immunotherapy has become the standard of care for non-small cell lung cancer (NSCLC) patients. Some patients experience primary resistance to immunotherapy. Currently, we lack a marker of resistance to immunotherapy. Myeloid-derived suppressive-like cells (MDSCs) can reduce tumor response rate and survival outcomes.

METHODS

This is an exploratory prospective observational study on metastatic NSCLC patients starting immunotherapy. Baseline peripheral blood samples were collected. Monocytic (M)-MDSCs were analyzed by flow cytometry. The main clinical outcomes were tumor response, progression-free survival (PFS), and overall survival (OS). The association between MDSC levels and tumor response was assessed. The association of PFS with OS was investigated using the Kaplan-Meier method and the Cox proportional hazards model.

RESULTS

Twenty-two patients were included. The median M-MDSC value was higher in patients with progressive disease than patients with stable disease or partial response, p = 0.045. The median MDSC value in the overall population was 1.9. We found worse PFS (HR = 2.51; p = 0.046) and OS (HR = 2.68; p = 0.042) in patients with M-MDSC values higher than the median.

CONCLUSIONS

In this exploratory analysis, high M-MDSC levels are strongly associated with primary resistance to immunotherapy. If validated in larger studies, MDSC levels in blood samples could help to select NSCLC patients for higher benefit from immunotherapy.

摘要

背景

免疫疗法已成为非小细胞肺癌（NSCLC）患者的标准治疗方法。有些患者对免疫疗法产生原发性耐药。目前，我们缺乏免疫治疗耐药的标志物。髓源性抑制性样细胞（MDSCs）可降低肿瘤的反应率和生存结果。

方法

这是一项针对开始免疫治疗的转移性 NSCLC 患者的探索性前瞻性观察研究。采集基线外周血样本。通过流式细胞术分析单核细胞（M）-MDSCs。主要临床结局为肿瘤反应、无进展生存期（PFS）和总生存期（OS）。评估 MDSC 水平与肿瘤反应之间的关系。使用 Kaplan-Meier 方法和 Cox 比例风险模型研究 PFS 与 OS 的关系。

结果

共纳入 22 例患者。与疾病稳定或部分缓解的患者相比，疾病进展患者的中位 M-MDSC 值更高，p = 0.045。总体人群的 MDSC 中位值为 1.9。我们发现，M-MDSC 值高于中位数的患者 PFS（HR = 2.51；p = 0.046）和 OS（HR = 2.68；p = 0.042）更差。

结论

在这项探索性分析中，高水平的 M-MDSC 与免疫治疗的原发性耐药密切相关。如果在更大规模的研究中得到验证，血液样本中的 MDSC 水平可能有助于选择从免疫治疗中获益更高的 NSCLC 患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6c5/9043492/d886e6eb9af1/fimmu-13-866561-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6c5/9043492/9d61b2b2fe05/fimmu-13-866561-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6c5/9043492/d560d818f622/fimmu-13-866561-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6c5/9043492/714339b6b619/fimmu-13-866561-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6c5/9043492/936d4742b5d0/fimmu-13-866561-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6c5/9043492/d886e6eb9af1/fimmu-13-866561-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6c5/9043492/9d61b2b2fe05/fimmu-13-866561-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6c5/9043492/d560d818f622/fimmu-13-866561-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6c5/9043492/714339b6b619/fimmu-13-866561-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6c5/9043492/936d4742b5d0/fimmu-13-866561-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6c5/9043492/d886e6eb9af1/fimmu-13-866561-g005.jpg

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