血清标记物预测免疫检查点抑制剂治疗晚期非小细胞肺癌疗效的研究进展
Progress in the Study of Serum Markers to Predict the Efficacy of Immune Checkpoint Inhibitors in the Treatment of Advanced Non-Small Cell Lung Cancer
DOI: 10.12677/acm.2024.1492547, PDF,   
作者: 李 颖：吉首大学医学院，湖南 吉首；湖南医药学院总医院肿瘤中心，湖南 怀化；田绍东*, 唐红兰：湖南医药学院总医院肿瘤中心，湖南 怀化；向明钧：吉首大学医学院，湖南 吉首
关键词: 非小细胞肺癌；免疫检查点抑制剂；外周血标记物；Non-Small Cell Lung Cancer； Immune Checkpoint Inhibitors； Peripheral Blood Marker
摘要: 免疫检查点抑制剂在晚期非小细胞肺癌中的应用显著提高了患者的生存获益，但是现在临床上没有明确对于免疫治疗疗效预测的标记物，常见的PDL1、CTLA-4只能通过组织活检获得，如果能证明外周血相关指标对于疗效的预测，会更简便或者与组织学综合考量后预测价值更高。本文将从血清标记物对免疫检查点抑制剂治疗晚期非小细胞肺癌预后基线及动态监测的相关研究进展进行综述。
Abstract: The application of immune checkpoint inhibitors in advanced non-small cell lung cancer has significantly improved the survival benefits of patients. However, there are no clear markers for predicting the efficacy of immunotherapy in clinical practice, and common PDL1 and CTA4 can only be obtained through tissue biopsy. If the prediction of efficacy of peripheral blood related indicators can be proved, the clinical curative effect can be more easily and dynamically predicted, or the predictive value of peripheral blood indicators combined with histology may be higher. This article reviews the progress of serum markers in baseline and dynamic monitoring of the prognosis of advanced non-small cell lung cancer treated with immune checkpoint inhibitors.
文章引用：李颖, 田绍东, 向明钧, 唐红兰. 血清标记物预测免疫检查点抑制剂治疗晚期非小细胞肺癌疗效的研究进展[J]. 临床医学进展, 2024, 14(9): 917-924. https://doi.org/10.12677/acm.2024.1492547

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] Duma, N., Santana-Davila, R. and Molina, J.R. (2019) Non-Small Cell Lung Cancer: Epidemiology, Screening, Diagnosis, and Treatment. Mayo Clinic Proceedings, 94, 1623-1640. [Google Scholar] [CrossRef] [PubMed]
[3] Kotecki, N., Vuagnat, P., O’Neil, B.H., Jalal, S., Rottey, S., Prenen, H., et al. (2021) A Phase I Study of an IDO-1 Inhibitor (LY3381916) as Monotherapy and in Combination with an Anti-PD-L1 Antibody (LY3300054) in Patients with Advanced Cancer. Journal of Immunotherapy, 44, 264-275. [Google Scholar] [CrossRef] [PubMed]
[4] Aggarwal, H., Ndirangu, K., Winfree, K.B., Muehlenbein, C.E., Zhu, E., Tongbram, V., et al. (2023) A Network Meta-Analysis of Immunotherapy-Based Treatments for Advanced Nonsquamous Non-Small Cell Lung Cancer. Journal of Comparative Effectiveness Research, 12, e220016. [Google Scholar] [CrossRef] [PubMed]
[5] Borst, J., Ahrends, T., Bąbała, N., Melief, C.J.M. and Kastenmüller, W. (2018) CD4+ T Cell Help in Cancer Immunology and Immunotherapy. Nature Reviews Immunology, 18, 635-647. [Google Scholar] [CrossRef] [PubMed]
[6] Gonzalez, H., Hagerling, C. and Werb, Z. (2018) Roles of the Immune System in Cancer: From Tumor Initiation to Metastatic Progression. Genes & Development, 32, 1267-1284. [Google Scholar] [CrossRef] [PubMed]
[7] Myers, J.A. and Miller, J.S. (2020) Exploring the NK Cell Platform for Cancer Immunotherapy. Nature Reviews Clinical Oncology, 18, 85-100. [Google Scholar] [CrossRef] [PubMed]
[8] Li, X., Lv, Q., Feng, Y., Gu, Y., Xia, R., Ma, J., et al. (2018) Interleukin-33, a Potential Cytokine Expressed in the Tumor Microenvironment Is Involved in Antitumor Immunotherapy through Facilitating CD8+ T Cells. Journal of Interferon & Cytokine Research, 38, 491-499. [Google Scholar] [CrossRef] [PubMed]
[9] van Montfoort, N., Borst, L., Korrer, M.J., Sluijter, M., Marijt, K.A., Santegoets, S.J., et al. (2018) NKG2A Blockade Potentiates CD8 T Cell Immunity Induced by Cancer Vaccines. Cell, 175, 1744-1755.E15. [Google Scholar] [CrossRef] [PubMed]
[10] Heng, J.S., Kim, J.M., Jones, D.K., Stoessel, K.M., Weiss, S.A., Sznol, M., et al. (2022) Autoimmune Retinopathy with Associated Anti-Retinal Antibodies as a Potential Immune-Related Adverse Event Associated with Immunotherapy in Patients with Advanced Cutaneous Melanoma: Case Series and Systematic Review. BMJ Open Ophthalmology, 7, e000889. [Google Scholar] [CrossRef] [PubMed]
[11] 郭莹, 高天慧, 赵孟阳, 等. 晚期非小细胞肺癌淋巴细胞亚群及细胞因子与免疫疗效的关系研究[J]. 中华全科医学, 2022, 20(9): 1462-1465.
[12] Kagamu, H., Kitano, S., Yamaguchi, O., Yoshimura, K., Horimoto, K., Kitazawa, M., et al. (2020) CD4+ T-Cell Immunity in the Peripheral Blood Correlates with Response to Anti-PD-1 Therapy. Cancer Immunology Research, 8, 334-344. [Google Scholar] [CrossRef] [PubMed]
[13] Kim, C.G., Hong, M.H., Kim, K.H., Seo, I., Ahn, B., Pyo, K., et al. (2021) Dynamic Changes in Circulating PD-1+CD8+ T Lymphocytes for Predicting Treatment Response to PD-1 Blockade in Patients with Non-Small-Cell Lung Cancer. European Journal of Cancer, 143, 113-126. [Google Scholar] [CrossRef] [PubMed]
[14] Youn, J., Park, S., Park, S., Kim, G., Lee, H., Son, J., et al. (2020) Peripheral Natural Killer Cells and Myeloid-Derived Suppressor Cells Correlate with Anti-PD-1 Responses in Non-Small Cell Lung Cancer. Scientific Reports, 10, Article No. 9050. [Google Scholar] [CrossRef] [PubMed]
[15] Isacco, C.G., Ballini, A., De Vito, D., Nguyen, K.C.D., Cantore, S., Bottalico, L., et al. (2021) Rebalancing the Oral Microbiota as an Efficient Tool in Endocrine, Metabolic and Immune Disorders. Endocrine, Metabolic & Immune Disorders-Drug Targets, 21, 777-784. [Google Scholar] [CrossRef] [PubMed]
[16] Soyano, A.E., Dholaria, B., Marin-Acevedo, J.A., Diehl, N., Hodge, D., Luo, Y., et al. (2018) Peripheral Blood Biomarkers Correlate with Outcomes in Advanced Non-Small Cell Lung Cancer Patients Treated with Anti-PD-1 Antibodies. Journal for ImmunoTherapy of Cancer, 6, Article 129. [Google Scholar] [CrossRef] [PubMed]
[17] Moschetta, M., Uccello, M., Kasenda, B., Mak, G., McClelland, A., Boussios, S., et al. (2017) Dynamics of Neutrophils-To-Lymphocyte Ratio Predict Outcomes of PD-1/PD-L1 Blockade. BioMed Research International, 2017, Article 1506824. [Google Scholar] [CrossRef] [PubMed]
[18] Russo, A., Russano, M., Franchina, T., Migliorino, M.R., Aprile, G., Mansueto, G., et al. (2020) Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Outcomes with Nivolumab in Pretreated Non-Small Cell Lung Cancer (NSCLC): A Large Retrospective Multicenter Study. Advances in Therapy, 37, 1145-1155. [Google Scholar] [CrossRef] [PubMed]
[19] Nakaya, A., Kurata, T., Yoshioka, H., Takeyasu, Y., Niki, M., Kibata, K., et al. (2018) Neutrophil-to-Lymphocyte Ratio as an Early Marker of Outcomes in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Nivolumab. International Journal of Clinical Oncology, 23, 634-640. [Google Scholar] [CrossRef] [PubMed]
[20] Kiriu, T., Yamamoto, M., Nagano, T., Hazama, D., Sekiya, R., Katsurada, M., et al. (2018) The Time-Series Behavior of Neutrophil-to-Lymphocyte Ratio Is Useful as a Predictive Marker in Non-Small Cell Lung Cancer. PLOS ONE, 13, e0193018. [Google Scholar] [CrossRef] [PubMed]
[21] Sánchez-Gastaldo, A., Muñoz-Fuentes, M.A., Molina-Pinelo, S., Alonso-García, M., Boyero, L. and Bernabé-Caro, R. (2021) Correlation of Peripheral Blood Biomarkers with Clinical Outcomes in NSCLC Patients with High PD-L1 Expression Treated with Pembrolizumab. Translational Lung Cancer Research, 10, 2509-2522. [Google Scholar] [CrossRef] [PubMed]
[22] Lu, X., Wan, J. and Shi, H. (2022) Platelet-to-Lymphocyte and Neutrophil-to-Lymphocyte Ratios Are Associated with the Efficacy of Immunotherapy in Stage III/IV Non-Small Cell Lung Cancer. Oncology Letters, 24, Article No. 266. [Google Scholar] [CrossRef] [PubMed]
[23] Tay, S.H., Toh, M.M.X., Thian, Y.L., Vellayappan, B.A., Fairhurst, A., Chan, Y.H., et al. (2022) Cytokine Release Syndrome in Cancer Patients Receiving Immune Checkpoint Inhibitors: A Case Series of 25 Patients and Review of the Literature. Frontiers in Immunology, 13, Article 807050. [Google Scholar] [CrossRef] [PubMed]
[24] Sillito, F., Holler, A. and Stauss, H.J. (2020) Engineering CD4+ T Cells to Enhance Cancer Immunity. Cells, 9, Article 1721. [Google Scholar] [CrossRef] [PubMed]
[25] Honrubia-Peris, B., Garde-Noguera, J., García-Sánchez, J., Piera-Molons, N., Llombart-Cussac, A. and Fernández-Murga, M.L. (2021) Soluble Biomarkers with Prognostic and Predictive Value in Advanced Non-Small Cell Lung Cancer Treated with Immunotherapy. Cancers, 13, Article 4280. [Google Scholar] [CrossRef] [PubMed]
[26] Liu, C., Yang, L., Xu, H., Zheng, S., Wang, Z., Wang, S., et al. (2022) Systematic Analysis of IL-6 as a Predictive Biomarker and Desensitizer of Immunotherapy Responses in Patients with Non-Small Cell Lung Cancer. BMC Medicine, 20, Article No. 187. [Google Scholar] [CrossRef] [PubMed]
[27] Hu, Y., Li, S., Xiao, H., Xiong, Y., Lu, X., Yang, X., et al. (2023) Distinct Circulating Cytokine/Chemokine Profiles Correlate with Clinical Benefit of Immune Checkpoint Inhibitor Monotherapy and Combination Therapy in Advanced Non‐Small Cell Lung Cancer. Cancer Medicine, 12, 12234-12252. [Google Scholar] [CrossRef] [PubMed]
[28] Ke, W., Zhang, L. and Dai, Y. (2020) The Role of IL‐6 in Immunotherapy of Non‐Small Cell Lung Cancer (NSCLC) with Immune‐Related Adverse Events (irAEs). Thoracic Cancer, 11, 835-839. [Google Scholar] [CrossRef] [PubMed]
[29] Sanmamed, M.F., Perez-Gracia, J.L., Schalper, K.A., Fusco, J.P., Gonzalez, A., Rodriguez-Ruiz, M.E., et al. (2017) Changes in Serum Interleukin-8 (IL-8) Levels Reflect and Predict Response to Anti-PD-1 Treatment in Melanoma and Non-Small-Cell Lung Cancer Patients. Annals of Oncology, 28, 1988-1995. [Google Scholar] [CrossRef] [PubMed]
[30] Cabel, L., Proudhon, C., Romano, E., Girard, N., Lantz, O., Stern, M., et al. (2018) Clinical Potential of Circulating Tumour DNA in Patients Receiving Anticancer Immunotherapy. Nature Reviews Clinical Oncology, 15, 639-650. [Google Scholar] [CrossRef] [PubMed]
[31] Nabet, B.Y., Esfahani, M.S., Moding, E.J., Hamilton, E.G., Chabon, J.J., Rizvi, H., et al. (2020) Noninvasive Early Identification of Therapeutic Benefit from Immune Checkpoint Inhibition. Cell, 183, 363-376.E13. [Google Scholar] [CrossRef] [PubMed]
[32] Anagnostou, V., Ho, C., Nicholas, G., Juergens, R.A., Sacher, A., Fung, A.S., et al. (2023) ctDNA Response after Pembrolizumab in Non-Small Cell Lung Cancer: Phase 2 Adaptive Trial Results. Nature Medicine, 29, 2559-2569. [Google Scholar] [CrossRef] [PubMed]
[33] Han, X., Tang, X., Zhu, H., Zhu, D., Zhang, X., Meng, X., et al. (2022) Short-Term Dynamics of Circulating Tumor DNA Predicting Efficacy of Sintilimab Plus Docetaxel in Second-Line Treatment of Advanced NSCLC: Biomarker Analysis from a Single-Arm, Phase 2 Trial. Journal for ImmunoTherapy of Cancer, 10, e004952. [Google Scholar] [CrossRef] [PubMed]
[34] Yue, D., Liu, W., Chen, C., Zhang, T., Ma, Y., Cui, L., et al. (2022) Circulating Tumor DNA Predicts Neoadjuvant Immunotherapy Efficacy and Recurrence-Free Survival in Surgical Non-Small Cell Lung Cancer Patients. Translational Lung Cancer Research, 11, 263-276. [Google Scholar] [CrossRef] [PubMed]
[35] Sharma, S., Zhuang, R., Long, M., Pavlovic, M., Kang, Y., Ilyas, A., et al. (2018) Circulating Tumor Cell Isolation, Culture, and Downstream Molecular Analysis. Biotechnology Advances, 36, 1063-1078. [Google Scholar] [CrossRef] [PubMed]
[36] Zhang, Y., Zheng, H., Zhan, Y., et al. (2018) Detection and Application of Circulating Tumor Cell and Circulating Tumor DNA in the Non-Small Cell Lung Cancer. American Journal of Cancer Research, 8, 2377-2386.
[37] Rzhevskiy, A., Kapitannikova, A., Malinina, P., Volovetsky, A., Aboulkheyr Es, H., Kulasinghe, A., et al. (2021) Emerging Role of Circulating Tumor Cells in Immunotherapy. Theranostics, 11, 8057-8075. [Google Scholar] [CrossRef] [PubMed]
[38] Zhou, Q., Liu, X., Li, J., Tong, B., Xu, Y., Chen, M., et al. (2023) Circulating Tumor Cells PD‐L1 Expression Detection and Correlation of Therapeutic Efficacy of Immune Checkpoint Inhibition in Advanced Non‐Small‐Cell Lung Cancer. Thoracic Cancer, 14, 470-478. [Google Scholar] [CrossRef] [PubMed]
[39] Strati, A., Economopoulou, P., Lianidou, E. and Psyrri, A. (2023) Clinical Significance of PD-L1 Status in Circulating Tumor Cells for Cancer Management during Immunotherapy. Biomedicines, 11, Article 1768. [Google Scholar] [CrossRef] [PubMed]
[40] Chalmers, Z.R., Connelly, C.F., Fabrizio, D., Gay, L., Ali, S.M., Ennis, R., et al. (2017) Analysis of 100,000 Human Cancer Genomes Reveals the Landscape of Tumor Mutational Burden. Genome Medicine, 9, Article No. 34. [Google Scholar] [CrossRef] [PubMed]
[41] Kim, E.S., Velcheti, V., Mekhail, T., Yun, C., Shagan, S.M., Hu, S., et al. (2022) Blood-Based Tumor Mutational Burden as a Biomarker for Atezolizumab in Non-Small Cell Lung Cancer: The Phase 2 B-F1RST Trial. Nature Medicine, 28, 939-945. [Google Scholar] [CrossRef] [PubMed]
[42] Wang, Z., Duan, J., Cai, S., Han, M., Dong, H., Zhao, J., et al. (2019) Assessment of Blood Tumor Mutational Burden as a Potential Biomarker for Immunotherapy in Patients with Non-Small Cell Lung Cancer with Use of a Next-Generation Sequencing Cancer Gene Panel. JAMA Oncology, 5, 696-702. [Google Scholar] [CrossRef] [PubMed]

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