• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验

自然杀伤细胞活性作为预测非小细胞肺癌免疫治疗反应的生物标志物的疗效。

Efficacy of natural killer cell activity as a biomarker for predicting immunotherapy response in non-small cell lung cancer.

机构信息

Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

出版信息

Thorac Cancer. 2020 Nov;11(11):3337-3345. doi: 10.1111/1759-7714.13677. Epub 2020 Oct 5.

DOI:10.1111/1759-7714.13677
PMID:33017518
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7606014/
Abstract

BACKGROUND

The establishment of biomarkers that can be used to predict the response to immunotherapy for malignancy is extremely important. In particular, noninvasive analysis of immune cells from peripheral blood before treatment has gained increased attention, and natural killer (NK) cell activity has been shown to be related to treatment response. Here, we aimed to confirm the relationship between the response to immunotherapy and NK cell activity.

METHODS

In this prospective observational study, patients with advanced NSCLC who were scheduled for immunotherapy from October 2018 to December 2019 were enrolled. Baseline NK cell activity was compared according to the best clinical response to immunotherapy.

RESULTS

A total of 54 patients with advanced NSCLC were enrolled, and 34 patients were analyzed. The baseline NK cell activity was significantly higher in the non-PD group than in the PD group (P = 0.002). At the cutoff level of ≥1200 pg/mL, baseline NK cell activity yielded a sensitivity of 80% and a specificity of 68.4% in predicting the response to immunotherapy (AUC = 0.8, P < 0.003). The median progression-free survival (PFS) was significantly better in the high NK group (P = 0.003), and correlation between baseline NK cell activity and PFS was also confirmed (r = 0.517, P = 0.002).

CONCLUSIONS

Baseline NK cell activity was related to the response to immunotherapy and the PFS. We suggest that NK cell activity from peripheral blood before immunotherapy is a noninvasive, simple, and novel way to predicting the treatment response in patients with NSCLC.

KEY POINTS

SIGNIFICANT FINDINGS OF THE STUDY: The response to immunotherapy was significantly better in patients with high baseline NK cell activity, and there was a significant correlation between baseline NK cell activity and PFS. What this study adds This study demonstrates the efficacy of baseline NK cell activity from peripheral blood as a biomarker for predicting immunotherapy response.

摘要

背景

建立可用于预测恶性肿瘤免疫治疗反应的生物标志物非常重要。特别是,治疗前外周血免疫细胞的非侵入性分析受到了越来越多的关注,并且已经表明自然杀伤 (NK) 细胞活性与治疗反应有关。在这里,我们旨在确认免疫治疗反应与 NK 细胞活性之间的关系。

方法

在这项前瞻性观察性研究中,纳入了 2018 年 10 月至 2019 年 12 月计划接受免疫治疗的晚期 NSCLC 患者。根据免疫治疗的最佳临床反应比较了基线 NK 细胞活性。

结果

共纳入 54 例晚期 NSCLC 患者,分析了 34 例患者。非 PD 组的基线 NK 细胞活性明显高于 PD 组(P = 0.002)。在 ≥1200 pg/mL 的截断水平,基线 NK 细胞活性预测免疫治疗反应的灵敏度为 80%,特异性为 68.4%(AUC = 0.8,P < 0.003)。高 NK 组的中位无进展生存期(PFS)明显更好(P = 0.003),并且还证实了基线 NK 细胞活性与 PFS 之间的相关性(r = 0.517,P = 0.002)。

结论

基线 NK 细胞活性与免疫治疗反应和 PFS 相关。我们建议,免疫治疗前外周血中的 NK 细胞活性是一种非侵入性、简单且新颖的方法,可以预测 NSCLC 患者的治疗反应。

关键点

研究的重要发现:基线 NK 细胞活性高的患者免疫治疗反应更好,并且基线 NK 细胞活性与 PFS 之间存在显著相关性。本研究的意义本研究证明了外周血基线 NK 细胞活性作为预测免疫治疗反应的生物标志物的功效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bf5/7606014/f6547470d4e2/TCA-11-3337-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bf5/7606014/e788ac45daf4/TCA-11-3337-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bf5/7606014/355a0002bfe7/TCA-11-3337-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bf5/7606014/393d50dbc308/TCA-11-3337-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bf5/7606014/f6547470d4e2/TCA-11-3337-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bf5/7606014/e788ac45daf4/TCA-11-3337-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bf5/7606014/355a0002bfe7/TCA-11-3337-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bf5/7606014/393d50dbc308/TCA-11-3337-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bf5/7606014/f6547470d4e2/TCA-11-3337-g004.jpg

相似文献

1
Efficacy of natural killer cell activity as a biomarker for predicting immunotherapy response in non-small cell lung cancer.自然杀伤细胞活性作为预测非小细胞肺癌免疫治疗反应的生物标志物的疗效。
Thorac Cancer. 2020 Nov;11(11):3337-3345. doi: 10.1111/1759-7714.13677. Epub 2020 Oct 5.
2
Pembrolizumab plus allogeneic NK cells in advanced non-small cell lung cancer patients.派姆单抗联合异体自然杀伤细胞治疗晚期非小细胞肺癌患者。
J Clin Invest. 2020 May 1;130(5):2560-2569. doi: 10.1172/JCI132712.
3
Peripheral NK cells identified as the predictor of response in extensive-stage small cell lung cancer patients treated with first-line immunotherapy plus chemotherapy.外周 NK 细胞可作为一线免疫治疗联合化疗治疗广泛期小细胞肺癌患者反应的预测指标。
Clin Transl Oncol. 2024 Oct;26(10):2522-2530. doi: 10.1007/s12094-024-03479-4. Epub 2024 Apr 25.
4
Natural Killer Cells as a Potential Biomarker for Predicting Immunotherapy Efficacy in Patients with Non-Small Cell Lung Cancer.自然杀伤细胞作为预测非小细胞肺癌患者免疫治疗疗效的潜在生物标志物。
Target Oncol. 2020 Apr;15(2):241-247. doi: 10.1007/s11523-020-00712-2.
5
Association of Survival and Immune-Related Biomarkers With Immunotherapy in Patients With Non-Small Cell Lung Cancer: A Meta-analysis and Individual Patient-Level Analysis.免疫治疗与非小细胞肺癌患者生存及免疫相关生物标志物的相关性:一项荟萃分析和个体患者水平分析。
JAMA Netw Open. 2019 Jul 3;2(7):e196879. doi: 10.1001/jamanetworkopen.2019.6879.
6
The circulating pool of functionally competent NK and CD8+ cells predicts the outcome of anti-PD1 treatment in advanced NSCLC.功能健全的 NK 和 CD8+ 细胞循环池可预测晚期 NSCLC 患者接受抗 PD-1 治疗的结局。
Lung Cancer. 2019 Jan;127:153-163. doi: 10.1016/j.lungcan.2018.11.038. Epub 2018 Nov 29.
7
A trial of autologous ex vivo-expanded NK cell-enriched lymphocytes with docetaxel in patients with advanced non-small cell lung cancer as second- or third-line treatment: phase IIa study.自体体外扩增 NK 细胞富集的淋巴细胞联合多西紫杉醇治疗二线或三线晚期非小细胞肺癌的临床试验:Ⅱa 期研究。
Anticancer Res. 2013 May;33(5):2115-22.
8
Peripheral natural killer cells and myeloid-derived suppressor cells correlate with anti-PD-1 responses in non-small cell lung cancer.外周自然杀伤细胞和髓系来源的抑制细胞与非小细胞肺癌的抗 PD-1 反应相关。
Sci Rep. 2020 Jun 3;10(1):9050. doi: 10.1038/s41598-020-65666-x.
9
Relationship between intestinal flora structure and metabolite analysis and immunotherapy efficacy in Chinese NSCLC patients.肠道菌群结构与代谢物分析与中国 NSCLC 患者免疫治疗疗效的关系。
Thorac Cancer. 2020 Jun;11(6):1621-1632. doi: 10.1111/1759-7714.13442. Epub 2020 Apr 23.
10
Circulating tumor cell as a biomarker for evaluating allogenic NK cell immunotherapy on stage IV non-small cell lung cancer.循环肿瘤细胞作为评估异基因自然杀伤细胞免疫疗法对IV期非小细胞肺癌疗效的生物标志物。
Immunol Lett. 2017 Nov;191:10-15. doi: 10.1016/j.imlet.2017.09.004. Epub 2017 Sep 12.

引用本文的文献

1
Neutrophil-to-lymphocyte ratio affects the impact of proton pump inhibitors on efficacy of immune checkpoint inhibitors in patients with non‑small-cell lung cancer.中性粒细胞与淋巴细胞比值影响质子泵抑制剂对非小细胞肺癌患者免疫检查点抑制剂疗效的作用。
Int J Clin Oncol. 2025 Sep 2. doi: 10.1007/s10147-025-02859-2.
2
Natural killer cells: the immune frontline against circulating tumor cells.自然杀伤细胞:抵御循环肿瘤细胞的免疫前线。
J Exp Clin Cancer Res. 2025 Apr 10;44(1):118. doi: 10.1186/s13046-025-03375-x.
3
Cellular plasticity and non-small cell lung cancer: role of T and NK cell immune evasion and acquisition of resistance to immunotherapies.

本文引用的文献

1
Natural Killer Cells as a Potential Biomarker for Predicting Immunotherapy Efficacy in Patients with Non-Small Cell Lung Cancer.自然杀伤细胞作为预测非小细胞肺癌患者免疫治疗疗效的潜在生物标志物。
Target Oncol. 2020 Apr;15(2):241-247. doi: 10.1007/s11523-020-00712-2.
2
Pemetrexed Enhances Membrane PD-L1 Expression and Potentiates T Cell-Mediated Cytotoxicity by Anti-PD-L1 Antibody Therapy in Non-Small-Cell Lung Cancer.培美曲塞增强非小细胞肺癌中膜程序性死亡配体1(PD-L1)的表达,并通过抗PD-L1抗体疗法增强T细胞介导的细胞毒性。
Cancers (Basel). 2020 Mar 12;12(3):666. doi: 10.3390/cancers12030666.
3
Predictive biomarkers and mechanisms underlying resistance to PD1/PD-L1 blockade cancer immunotherapy.
细胞可塑性与非小细胞肺癌:T细胞和NK细胞免疫逃逸及对免疫疗法耐药性获得的作用
Cancer Metastasis Rev. 2025 Jan 25;44(1):27. doi: 10.1007/s10555-025-10244-8.
4
Comprehensive molecular characterization to predict immunotherapy response in advanced biliary tract cancer: a phase II trial of pembrolizumab.预测晚期胆管癌免疫治疗反应的综合分子特征分析:帕博利珠单抗的II期试验
Oncol Res. 2024 Dec 20;33(1):57-65. doi: 10.32604/or.2024.049054. eCollection 2025.
5
Natural Killer Cells in Cancers of Respiratory System and Their Applications in Therapeutic Approaches.自然杀伤细胞在呼吸系统癌症中的作用及其在治疗方法中的应用。
Immun Inflamm Dis. 2024 Nov;12(11):e70079. doi: 10.1002/iid3.70079.
6
Interferon-Gamma Secretion Is Significantly Decreased in Stage III Breast Cancer Patients.III期乳腺癌患者的干扰素-γ分泌显著降低。
Int J Mol Sci. 2024 Apr 22;25(8):4561. doi: 10.3390/ijms25084561.
7
Plasmacytoid Dendritic Cell, Slan-Monocyte and Natural Killer Cell Counts Function as Blood Cell-Based Biomarkers for Predicting Responses to Immune Checkpoint Inhibitor Monotherapy in Non-Small Cell Lung Cancer Patients.浆细胞样树突状细胞、Slan单核细胞和自然杀伤细胞计数作为基于血细胞的生物标志物,用于预测非小细胞肺癌患者对免疫检查点抑制剂单药治疗的反应。
Cancers (Basel). 2023 Nov 3;15(21):5285. doi: 10.3390/cancers15215285.
8
The influence of anti-cancer therapies on lymphocyte subpopulations of lung cancer patients.抗癌治疗对肺癌患者淋巴细胞亚群的影响。
Front Immunol. 2023 Aug 28;14:1239097. doi: 10.3389/fimmu.2023.1239097. eCollection 2023.
9
NK cell activity and methylated HOXA9 ctDNA as prognostic biomarkers in patients with non-small cell lung cancer treated with PD-1/PD-L1 inhibitors.NK 细胞活性和甲基化 HOXA9 ctDNA 作为 PD-1/PD-L1 抑制剂治疗非小细胞肺癌患者的预后生物标志物。
Br J Cancer. 2023 Jul;129(1):135-142. doi: 10.1038/s41416-023-02285-z. Epub 2023 May 3.
10
Mass Cytometry Reveals Classical Monocytes, NK Cells, and ICOS+ CD4+ T Cells Associated with Pembrolizumab Efficacy in Patients with Lung Cancer.质谱细胞术揭示了与肺癌患者接受派姆单抗治疗疗效相关的经典单核细胞、NK 细胞和 ICOS+CD4+T 细胞。
Clin Cancer Res. 2022 Dec 1;28(23):5136-5148. doi: 10.1158/1078-0432.CCR-22-1386.
预测生物标志物和抗 PD1/PD-L1 阻断癌症免疫治疗的机制。
Mol Cancer. 2020 Jan 30;19(1):19. doi: 10.1186/s12943-020-1144-6.
4
Peripheral immune-based biomarkers in cancer immunotherapy: can we realize their predictive potential?癌症免疫治疗中的外周免疫相关生物标志物:我们能否实现其预测潜能?
J Immunother Cancer. 2019 Nov 27;7(1):325. doi: 10.1186/s40425-019-0799-2.
5
PD/1-PD-Ls Checkpoint: Insight on the Potential Role of NK Cells.PD-1/PD-Ls 检查点:NK 细胞潜在作用的新见解。
Front Immunol. 2019 Jun 4;10:1242. doi: 10.3389/fimmu.2019.01242. eCollection 2019.
6
Tumor mutational load predicts survival after immunotherapy across multiple cancer types.肿瘤突变负荷可预测多种癌症类型免疫治疗后的生存情况。
Nat Genet. 2019 Feb;51(2):202-206. doi: 10.1038/s41588-018-0312-8. Epub 2019 Jan 14.
7
Immune checkpoint inhibitors: recent progress and potential biomarkers.免疫检查点抑制剂:最新进展与潜在生物标志物。
Exp Mol Med. 2018 Dec 13;50(12):1-11. doi: 10.1038/s12276-018-0191-1.
8
Predictive biomarkers of response for immune checkpoint inhibitors in non-small-cell lung cancer.免疫检查点抑制剂在非小细胞肺癌中的反应预测生物标志物。
Eur J Cancer. 2019 Jan;106:144-159. doi: 10.1016/j.ejca.2018.11.002. Epub 2018 Dec 5.
9
PD-L1 blockade enhances anti-tumor efficacy of NK cells.程序性死亡配体1(PD-L1)阻断增强自然杀伤(NK)细胞的抗肿瘤功效。
Oncoimmunology. 2018 Aug 27;7(11):e1509819. doi: 10.1080/2162402X.2018.1509819. eCollection 2018.
10
The IFN-γ/PD-L1 axis between T cells and tumor microenvironment: hints for glioma anti-PD-1/PD-L1 therapy.T 细胞与肿瘤微环境之间的 IFN-γ/PD-L1 轴:胶质母细胞瘤抗 PD-1/PD-L1 治疗的提示。
J Neuroinflammation. 2018 Oct 17;15(1):290. doi: 10.1186/s12974-018-1330-2.