外周血指标在PD-L1低表达晚期非小细胞肺癌免疫治疗疗效评价中作用分析
Analysis of the Role of Peripheral Blood Indicators in Evaluating the Efficacy of Immunotherapy for Advanced NSCLC with Low PD-L1 Expression
DOI: 10.12677/acm.2026.163970, PDF,   
作者: 陆海燕：海军青岛特勤疗养中心门诊部，山东 青岛；路 中*：山东第二医科大学附属医院肿瘤内科，山东 潍坊
关键词: 非小细胞肺癌；PD-L1低表达；免疫治疗；外周血液标志物；疗效预测；Non-Small Cell Lung Cancer； PD-L1 Low Expression； Immunotherapy； Peripheral Blood Biomarkers； Efficacy Prediction
摘要: 晚期非小细胞肺癌(NSCLC)是全球癌症相关死亡的主要原因。免疫检查点抑制剂(ICIs)彻底改变了驱动基因阴性晚期NSCLC的治疗格局，但其疗效与程序性死亡配体1 (PD-L1)的表达水平密切相关。PD-L1低表达患者群体庞大，其一线免疫治疗疗效有限且异质性高，因此迫切需要可靠的生物标志物来指导治疗决策。近年来，外周血液标志物因其无创、简便、可动态监测的独特优势而备受关注。本综述系统分析了改良格拉斯哥预后评分(mGPS)、C反应蛋白(CRP)、C反应蛋白与白蛋白比值(CAR)、血小板与淋巴细胞比率(PLR)、中性粒细胞与淋巴细胞比值(NLR)以及乳酸脱氢酶(LDH)等外周血液标志物，在PD-L1低表达晚期NSCLC一线免疫治疗疗效评价与预后预测中的价值。现有证据表明，这些标志物与患者的生存预后和治疗反应显著相关，展现出巨大的应用潜力。动态监测这些指标有助于早期识别潜在获益人群或治疗耐药，从而为PD-L1低表达这一临床难题提供个体化治疗的决策依据，最终优化治疗策略。
Abstract: Advanced non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality worldwide. While immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape for driver-gene-negative advanced NSCLC, their efficacy is closely tied to programmed death-ligand 1 (PD-L1) expression levels. A significant proportion of patients with low PD-L1 expression derive limited and heterogeneous benefit from first-line immunotherapy, creating a pressing need for reliable biomarkers to guide treatment decisions. In recent years, peripheral blood biomarkers have garnered considerable attention due to their non-invasive, convenient, and dynamically monitorable advantages. This review comprehensively analyzes the role of various peripheral blood biomarkers—including the modified Glasgow Prognostic Score (mGPS), C-reactive protein (CRP), CRP-to-albumin ratio (CAR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and lactate dehydrogenase (LDH)—in evaluating the efficacy and predicting outcomes of first-line immunotherapy in PD-L1 low-expression advanced NSCLC. Accumulated evidence indicates that these biomarkers are significantly associated with patient survival and treatment response, demonstrating considerable potential for clinical application. Dynamic monitoring of these markers could facilitate the early identification of patients who are likely to benefit or develop resistance, thereby informing personalized treatment strategies for the clinically challenging PD-L1 low-expression population and ultimately optimizing therapeutic approaches.
文章引用：陆海燕, 路中. 外周血指标在PD-L1低表达晚期非小细胞肺癌免疫治疗疗效评价中作用分析[J]. 临床医学进展, 2026, 16(3): 1845-1853. https://doi.org/10.12677/acm.2026.163970

参考文献

[1] Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A., et al. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71, 209-249. [Google Scholar] [CrossRef] [PubMed]
[2] 郑荣寿, 陈茹, 韩冰峰, 等. 2022年中国恶性肿瘤流行情况分析[J]. 中华肿瘤杂志, 2024, 46(3): 221-231.
[3] Lahiri, A., Maji, A., Potdar, P.D., Singh, N., Parikh, P., Bisht, B., et al. (2023) Lung Cancer Immunotherapy: Progress, Pitfalls, and Promises. Molecular Cancer, 22, Article 40. [Google Scholar] [CrossRef] [PubMed]
[4] Hanna, N.H., Robinson, A.G., Temin, S., et al. (2021) Therapy for Stage IV Non-Small-Cell Lung Cancer with Driver Alterations: ASCO and OH (CCO) Joint Guideline Update. Journal of Clinical Oncology, 39, 1040-1091.
[5] 郭寒菲, 白日兰, 崔久嵬. 肺癌免疫检查点抑制剂的联合治疗研究进展[J]. 中国肺癌杂志, 2020, 23(2): 101-110.
[6] 赵坤, 苗健龙, 屈光义. 免疫检查点抑制剂在PD-L1低表达/阴性晚期NSCLC患者中的治疗现状[J]. 临床医学进展, 2023, 13(5): 8248-8253.
[7] 贾漫漫, 李纪宾, 林华, 邹小农, 赵平. 吸烟对男性肺癌患者组织学分型的影响及其趋势分析[J]. 中国肺癌杂志, 2017, 20(8): 516-521.
[8] Wang, X., Ricciuti, B., Alessi, J.V., Nguyen, T., Awad, M.M., Lin, X., et al. (2021) Smoking History as a Potential Predictor of Immune Checkpoint Inhibitor Efficacy in Metastatic Non-Small Cell Lung Cancer. JNCI: Journal of the National Cancer Institute, 113, 1761-1769. [Google Scholar] [CrossRef] [PubMed]
[9] Wang, C., Yu, Q., Song, T., Wang, Z., Song, L., Yang, Y., et al. (2022) The Heterogeneous Immune Landscape between Lung Adenocarcinoma and Squamous Carcinoma Revealed by Single-Cell RNA Sequencing. Signal Transduction and Targeted Therapy, 7, Article No. 289. [Google Scholar] [CrossRef] [PubMed]
[10] de Visser, K.E. and Joyce, J.A. (2023) The Evolving Tumor Microenvironment: From Cancer Initiation to Metastatic Outgrowth. Cancer Cell, 41, 374-403. [Google Scholar] [CrossRef] [PubMed]
[11] 石岩, 吕望, 汪路明, 胡坚. 肺癌驱动基因与PD-1/PD-L1信号通路相互作用在非小细胞肺癌发生发展中的研究进展[J]. 中国肺癌杂志, 2017, 20(11): 781-786.
[12] Reck, M., Rodríguez-Abreu, D., Robinson, A.G., Hui, R., Csőszi, T., Fülöp, A., et al. (2019) Updated Analysis of KEYNOTE-024: Pembrolizumab versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer with PD-L1 Tumor Proportion Score of 50% or Greater. Journal of Clinical Oncology, 37, 537-546. [Google Scholar] [CrossRef] [PubMed]
[13] Mok, T.S.K., Wu, Y., Kudaba, I., Kowalski, D.M., Cho, B.C., Turna, H.Z., et al. (2019) Pembrolizumab versus Chemotherapy for Previously Untreated, Pd-L1-Expressing, Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (KEYNOTE-042): A Randomised, Open-Label, Controlled, Phase 3 Trial. The Lancet, 393, 1819-1830. [Google Scholar] [CrossRef] [PubMed]
[14] de Castro, G., Kudaba, I., Wu, Y., Lopes, G., Kowalski, D.M., Turna, H.Z., et al. (2023) Five-Year Outcomes with Pembrolizumab versus Chemotherapy as First-Line Therapy in Patients with Non-Small-Cell Lung Cancer and Programmed Death Ligand-1 Tumor Proportion Score ≥ 1% in the KEYNOTE-042 Study. Journal of Clinical Oncology, 41, 1986-1991. [Google Scholar] [CrossRef] [PubMed]
[15] Garassino, M.C., Gadgeel, S., Speranza, G., Felip, E., Esteban, E., Dómine, M., et al. (2023) Pembrolizumab Plus Pemetrexed and Platinum in Nonsquamous Non-Small-Cell Lung Cancer: 5-Year Outcomes from the Phase 3 KEYNOTE-189 Study. Journal of Clinical Oncology, 41, 1992-1998. [Google Scholar] [CrossRef] [PubMed]
[16] Herbst, R.S., Giaccone, G., de Marinis, F., Reinmuth, N., Vergnenegre, A., Barrios, C.H., et al. (2020) Atezolizumab for First-Line Treatment of PD-L1-Selected Patients with NSCLC. New England Journal of Medicine, 383, 1328-1339. [Google Scholar] [CrossRef] [PubMed]
[17] Borghaei, H., Langer, C.J., Paz-Ares, L., Rodríguez-Abreu, D., Halmos, B., Garassino, M.C., et al. (2020) Pembrolizumab Plus Chemotherapy versus Chemotherapy Alone in Patients with Advanced Non-Small Cell Lung Cancer without Tumor PD-L1 Expression: A Pooled Analysis of 3 Randomized Controlled Trials. Cancer, 126, 4867-4877. [Google Scholar] [CrossRef] [PubMed]
[18] Reck, M., Rodríguez-Abreu, D., Robinson, A.G., Hui, R., Csőszi, T., Fülöp, A., et al. (2016) Pembrolizumab versus Chemotherapy for Pd-L1-Positive Non-Small-Cell Lung Cancer. New England Journal of Medicine, 375, 1823-1833. [Google Scholar] [CrossRef] [PubMed]
[19] Singh, R., Mishra, M.K. and Aggarwal, H. (2017) Inflammation, Immunity, and Cancer. Mediators of Inflammation, 2017, Article 6027305. [Google Scholar] [CrossRef] [PubMed]
[20] Gabrilovich, D.I. and Nagaraj, S. (2009) Myeloid-Derived Suppressor Cells as Regulators of the Immune System. Nature Reviews Immunology, 9, 162-174. [Google Scholar] [CrossRef] [PubMed]
[21] Yang, X., Tang, Z., Zhang, P., et al. (2019) Research Advances of JAK/STAT Signaling Pathway in Lung Cancer. Chinese Journal of Lung Cancer, 22, 45-51.
[22] 牛涛, 周逢海. 炎症与肿瘤微环境[J]. 中南大学学报(医学版), 2023, 48(12): 1899-1913.
[23] Andrews, L.P., Marciscano, A.E., Drake, C.G. and Vignali, D.A.A. (2017) LAG3 (CD223) as a Cancer Immunotherapy Target. Immunological Reviews, 276, 80-96. [Google Scholar] [CrossRef] [PubMed]
[24] 柯萍, 江波, 何文杰, 等. 外周血生物标志物与PD-1/PD-L1抑制剂治疗肺癌疗效的相关性[J]. 肿瘤防治研究, 2021, 48(11): 1006-1011.
[25] 姜战胜, 潘战宇, 任秀宝. PD-1/PD-L1抑制剂在晚期非小细胞肺癌中的治疗进展[J]. 中国肺癌杂志, 2017, 20(2): 138-142.
[26] Klümper, N., Saal, J., Berner, F., Lichtensteiger, C., Wyss, N., Heine, A., et al. (2022) C Reactive Protein Flare Predicts Response to Checkpoint Inhibitor Treatment in Non-Small Cell Lung Cancer. Journal for ImmunoTherapy of Cancer, 10, e004024. [Google Scholar] [CrossRef] [PubMed]
[27] Koh, Y.W. and Lee, H.W. (2017) Prognostic Impact of C-Reactive Protein/Albumin Ratio on the Overall Survival of Patients with Advanced Non-Small Cell Lung Cancers Receiving Palliative Chemotherapy. Medicine, 96, e6848. [Google Scholar] [CrossRef] [PubMed]
[28] Araki, T., Tateishi, K., Sonehara, K., Hirota, S., Komatsu, M., Yamamoto, M., et al. (2021) Clinical Utility of the C-Reactive Protein: Albumin Ratio in Non-Small Cell Lung Cancer Patients Treated with Nivolumab. Thoracic Cancer, 12, 603-612. [Google Scholar] [CrossRef] [PubMed]
[29] Ogura, Y., Kataoka, N., Kunimatsu, Y., Tachibana, Y., Sugimoto, T., Tani, N., et al. (2021) Predictors of Survival among Japanese Patients Receiving First-Line Chemoimmunotherapy for Advanced Non-Small Cell Lung Cancer. Thoracic Cancer, 12, 97-105. [Google Scholar] [CrossRef] [PubMed]
[30] Inoue, T., Tamiya, M., Tamiya, A., Nakahama, K., Taniguchi, Y., Shiroyama, T., et al. (2018) Analysis of Early Death in Japanese Patients with Advanced Non-Small-Cell Lung Cancer Treated with Nivolumab. Clinical Lung Cancer, 19, e171-e176. [Google Scholar] [CrossRef] [PubMed]
[31] Zhou, K., Cao, J., Lin, H., Liang, L., Shen, Z., Wang, L., et al. (2022) Prognostic Role of the Platelet to Lymphocyte Ratio (PLR) in the Clinical Outcomes of Patients with Advanced Lung Cancer Receiving Immunotherapy: A Systematic Review and Meta-Analysis. Frontiers in Oncology, 12, Article 962173. [Google Scholar] [CrossRef] [PubMed]
[32] 夏经纬, 陈羽中, 温少迪, 等. 外周血炎症指标作为预测性指标在晚期非小细胞肺癌免疫治疗中的应用[J]. 中国肺癌杂志, 2021, 24(9): 632-645.
[33] Ksienski, D., Wai, E.S., Alex, D., Croteau, N.S., Freeman, A.T., Chan, A., et al. (2021) Prognostic Significance of the Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio for Advanced Non-Small Cell Lung Cancer Patients with High PD-L1 Tumor Expression Receiving Pembrolizumab. Translational Lung Cancer Research, 10, 355-367. [Google Scholar] [CrossRef] [PubMed]
[34] 芦佳骏, 樊海宁, 宾任. 血清生物标志物对肝细胞癌的早期诊断及预后的应用[J]. 临床医学进展, 2022, 12(6): 5446-5453.
[35] Dan, J., Zhang, Y., Peng, Z., Huang, J., Gao, H., Xu, L., et al. (2013) Postoperative Neutrophil-to-Lymphocyte Ratio Change Predicts Survival of Patients with Small Hepatocellular Carcinoma Undergoing Radiofrequency Ablation. PLOS ONE, 8, e58184. [Google Scholar] [CrossRef] [PubMed]
[36] Chen, Y., Wen, S., Xia, J., Du, X., Wu, Y., Pan, B., et al. (2021) Association of Dynamic Changes in Peripheral Blood Indexes with Response to PD-1 Inhibitor-Based Combination Therapy and Survival among Patients with Advanced Non-Small Cell Lung Cancer. Frontiers in Immunology, 12, Article 672271. [Google Scholar] [CrossRef] [PubMed]
[37] 姜妮, 乔国梁, 王小利, 等. 中性粒细胞与淋巴细胞比例对评估接受过继性细胞免疫治疗的晚期胰腺癌患者预后的临床意义[J]. 北京大学学报(医学版), 2020, 52(3): 597-602.
[38] 王浩澄, 单东凤, 董娅, 杨雪, 于壮. 手术前后血清LDH浓度与大细胞神经内分泌肺癌患者手术预后的相关性分析[J]. 中国肺癌杂志, 2021, 24(5): 351-356.
[39] Zhang, Z., Li, Y., Yan, X., Song, Q., Wang, G., Hu, Y., et al. (2019) Pretreatment Lactate Dehydrogenase May Predict Outcome of Advanced Non-Small-Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors: A Meta-Analysis. Cancer Medicine, 8, 1467-1473. [Google Scholar] [CrossRef] [PubMed]
[40] Peng, L., Wang, Y., Liu, F., Qiu, X., Zhang, X., Fang, C., et al. (2020) Peripheral Blood Markers Predictive of Outcome and Immune-Related Adverse Events in Advanced Non-Small Cell Lung Cancer Treated with PD-1 Inhibitors. Cancer Immunology, Immunotherapy, 69, 1813-1822. [Google Scholar] [CrossRef] [PubMed]
[41] Sun, T., Chen, Z., Wei, K., et al. (2024) Research Progress on Predictive Biomarkers of Immunotherapy Efficacy
in Non-Small Cell Lung Cancer. Chinese Journal of Lung Cancer, 27, 459-465.
[42] Yuh, Y.J. and Kim, S.R. (2002) Actate Dehydrogenase (LDH) as a Tumor Marker for Non-Small Cell Lung Cancer. Cancer Research and Treatment, 34, 339-344. [Google Scholar] [CrossRef] [PubMed]

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