Detection of PD-L1 in circulating tumor cells of non-small cell lung cancer and its clinical applications

doi:10.3760/cma.j.cn371439-20250312-00110

Abstract

Abstract:

Non-small cell lung cancer （NSCLC） is a malignant tumor with a high global incidence rate， accounting for about 10.54% of all new cancer cases and posing a serious threat to human health. Due to significant individual variations in the efficacy of immunotherapy among NSCLC patients， it is necessary to identify accurate detection indicators to screen appropriate populations， monitor treatment efficacy， and assist in prognosis assessment. Programmed death-ligand 1 （PD-L1）， as an immunosuppressive molecule expressed on the surface of tumor cells and various immune cell membranes， can serve as a "companion diagnostic" or "supplementary diagnostic" tool to guide clinical treatment decisions for metastatic NSCLC patients. Given that tumor tissue PD-L1 testing is an invasive procedure and its reliability is still under debate， the assessment of PD-L1 expression via liquid biopsies， such as circulating tumor cells， will play a significant role in predicting treatment response and prognosis in NSCLC patients.

Key words: Carcinoma， non-small-cell lung, Neoplastic cells， circulating, B7-H1 antigen, Detection techniques

Song Ziyan, Zhang Wenjing, Wang Zhendan, Zhao Zhikun, Ma Ying, Li Sheng. Detection of PD-L1 in circulating tumor cells of non-small cell lung cancer and its clinical applications[J]. Journal of International Oncology, 2025, 52(10): 641-645.

References 28

[1]	Li C, Lei S, Ding L, et al. Global burden and trends of lung cancer incidence and mortality[J]. Chin Med J (Engl), 2023, 136(13): 1583-1590. DOI: 10.1097/CM9.0000000000002529.
[2]	Parvez A, Choudhary F, Mudgal P, et al. PD-1 and PD-L1: architects of immune symphony and immunotherapy breakthroughs in cancer treatment[J]. Front Immunol, 2023, 14: 1296341. DOI: 10.3389/fimmu.2023.1296341.
[3]	邓隽军, 赵大勇, 李淼. 免疫检查点抑制剂在非小细胞肺癌治疗中的不良反应及危险因素[J]. 国际肿瘤学杂志, 2023, 50(9): 564-568. DOI: 10.3760/cma.j.cn371439-20230404-00108.
[4]	Riely GJ, Wood DE, Ettinger DS, et al. Non-small cell lung cancer, version 4.2024, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2024, 22(4): 249-274. DOI: 10.6004/jnccn.2204.0023.
[5]	Ettinger DS, Wood DE, Aisner DL, et al. Non-small cell lung cancer, version 3.2022, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2022, 20(5): 497-530. DOI: 10.6004/jnccn.2022.0025.
[6]	Gompelmann D, Sarova P, Mosleh B, et al. PD-L1 assessment in lung cancer biopsies-pitfalls and limitations[J]. Int J Biol Markers, 2024, 39(1): 3-8. DOI: 10.1177/03936155231214273.
[7]	Ring A, Nguyen-Sträuli BD, Wicki A, et al. Biology,vulnerabilities and clinical applications of circulating tumour cells[J]. Nat Rev Cancer, 2023, 23(2): 95-111. DOI: 10.1038/s41568-022-00536-4.
[8]	Pantazaka E, Ntzifa A, Roumeliotou A, et al. PD-L1/pS6 in cir-culating tumor cells (CTCs) during osimertinib treatment in patients with non-small cell lung cancer (NSCLC)[J]. Biomedicines, 2022, 10(8): 1893. DOI: 10.3390/biomedicines10081893.
[9]	Ikeda M, Koh Y, Teraoka S, et al. Longitudinal evaluation of PD-L1 expression on circulating tumor cells in non-small cell lung cancer patients treated with nivolumab[J]. Cancers (Basel), 2021, 13(10): 2290. DOI: 10.3390/cancers13102290.
[10]	Sinoquet L, Jacot W, Quantin X, et al. Liquid biopsy and immuno-oncology for advanced nonsmall cell lung cancer[J]. Clin Chem, 2023, 69(1): 23-40. DOI: 10.1093/clinchem/hvac166.
[11]	Cheng Y, Wang T, Lv X, et al. Detection of PD-L1 expression and its clinical significance in circulating tumor cells from patients with non-small-cell lung cancer[J]. Cancer Manag Res, 2020, 12: 2069-2078. DOI: 10.2147/CMAR.S245425. pmid: 32256114
[12]	Janning M, Kobus F, Babayan A, et al. Determination of PD-L1 expression in circulating tumor cells of NSCLC patients and correlation with response to PD-1/PD-L1 inhibitors[J]. Cancers (Basel), 2019, 11(6): 835. DOI: 10.3390/cancers11060835.
[13]	Schehr JL, Schultz ZD, Warrick JW, et al. High specificity in circulating tumor cell identification is required for accurate evaluation of programmed death-ligand 1[J]. PLoS One, 2016, 11(7): e0159397. DOI: 10.1371/journal.pone.0159397.
[14]	Liu Q, Zhao C, Jiang P, et al. Circulating tumor cells counts are associated with CD8⁺ T cell levels in programmed death-ligand 1-negative non-small cell lung cancer patients after radiotherapy: a retrospective study[J]. Medicine (Baltimore), 2021, 100(29): e26674. DOI: 10.1097/MD.0000000000026674.
[15]	Dong J, Zhu D, Tang X, et al. Circulating tumor cells in pulmonary vein and peripheral arterial provide a metric for PD-L1 diagnosis and prognosis of patients with non-small cell lung cancer[J]. PLoS One, 2019, 14(7): e0220306. DOI: 10.1371/journal.pone.0220306.
[16]	Cohen EN, Jayachandran G, Gao H, et al. Gene expression profiling of circulating tumor cells captured by MicroCavity Array is superior to enumeration in demonstrating therapy response in patients with newly diagnosed advanced and locally advanced non-small cell lung cancer[J]. Transl Lung Cancer Res, 2023, 12(1): 109-126. DOI: 10.21037/tlcr-22-314.
[17]	Ntzifa A, Strati A, Kallergi G, et al. Gene expression in circulating tumor cells reveals a dynamic role of EMT and PD-L1 during osimertinib treatment in NSCLC patients[J]. Sci Rep, 2021, 11(1): 2313. DOI: 10.1038/s41598-021-82068-9.
[18]	Rafli R, Harahap WA, Gondhowiardjo S, et al. Investigating radiotherapy effects on PD-L1 expression in circulating tumor cells: an exploratory study[J]. Asian Pac J Cancer Prev, 2024, 25(5): 1559-1566. DOI: 10.31557/APJCP.2024.25.5.1559.
[19]	Teo J, Mirenska A, Tan M, et al. A preliminary study for the assessment of PD-L1 and PD-L2 on circulating tumor cells by microfluidic-based chipcytometry[J]. Future Sci OA, 2017, 3(4): FSO244. DOI: 10.4155/fsoa-2017-0079.
[20]	Lantuejoul S, Sound-Tsao M, Cooper WA, et al. PD-L1 testing for lung cancer in 2019: perspective from the IASLC pathology committee[J]. J Thorac Oncol, 2020, 15(4): 499-519. DOI: 10.1016/j.jtho.2019.12.107. pmid: 31870882
[21]	Cai S, Deng Y, Wang Z, et al. Development and clinical validation of a microfluidic-based platform for CTC enrichment and downstream molecular analysis[J]. Front Oncol, 2023, 13: 1238332. DOI: 10.3389/fonc.2023.1238332.
[22]	Ilié M, Szafer-Glusman E, Hofman V, et al. Detection of PD-L1 in circulating tumor cells and white blood cells from patients with advanced non-small-cell lung cancer[J]. Ann Oncol, 2018, 29(1): 193-199. DOI: 10.1093/annonc/mdx636. pmid: 29361135
[23]	Dall'Olio FG, Gelsomino F, Conci N, et al. PD-L1 expression in circulating tumor cells as a promising prognostic biomarker in advanced non-small-cell lung cancer treated with immune checkpoint inhibitors[J]. Clin Lung Cancer, 2021, 22(5): 423-431. DOI: 10.1016/j.cllc.2021.03.005. pmid: 33849808
[24]	Zhou Q, Liu X, Li J, et al. Circulating tumor cells PD-L1 expression detection and correlation of therapeutic efficacy of immune checkpoint inhibition in advanced non-small-cell lung cancer[J]. Thorac Cancer, 2023, 14(5): 470-478. DOI: 10.1111/1759-7714.14767. pmid: 36630992
[25]	孔祥楠, 张茹, 宋欣新, 等. 非小细胞肺癌患者肺静脉血循环肿瘤细胞数量及程序性死亡受体配体-1表达与预后的关系[J]. 中华实用诊断与治疗杂志, 2021, 35(11): 1100-1103. DOI: 10.13507/j.issn.1674-3474.2021.11.006.
[26]	王伟. PD-L1在非小细胞肺癌外周血循环肿瘤细胞中的表达与分析[D]. 重庆: 重庆医科大学, 2021. DOI: 10.27674/d.cnki.gcyku. 2021.001000.
[27]	Dong J, Zhu D, Tang X, et al. Detection of circulating tumor cell molecular subtype in pulmonary vein predicting prognosis of stage Ⅰ-Ⅲ non-small cell lung cancer patients[J]. Front Oncol, 2019, 9: 1139. DOI: 10.3389/fonc.2019.01139.
[28]	Schehr JL, Sethakorn N, Schultz ZD, et al. Analytical validation and initial clinical testing of quantitative microscopic evaluation for PD-L1 and HLA Ⅰ expression on circulating tumor cells from patients with non-small cell lung cancer[J]. Biomark Res, 2022, 10(1): 26. DOI: 10.1186/s40364-022-00370-8.