Department of Pathology, Medical University of Warsaw, Pawinskiego 7 Street, 02-106, Warsaw, Poland.
Department of Internal Medicine and Hematology Laboratory of Flow Cytometry, u, Szaserow 128 Street, 04-141, Warsaw, Poland.
Stem Cell Rev Rep. 2019 Apr;15(2):324-330. doi: 10.1007/s12015-018-9860-7.
An immunotherapy was found to be effective in achieving long-term survival in some lung cancer patients. It has emerged to searching for new immune biomarkers for select the best candidates to this therapy. It is suggested that cancer stem cells (CSCs) are responsible for tumor initiation, maintenance and its metastatic potential. However, a role of CSCs in escape of cancer from immunosurveillance is unknown. The aim of the study was assess the phenotype of putative CSCs and to examine the expression of PD-L1 on CSCs in metastatic lymph nodes (LNs) in lung cancer patients.
Flow cytometry was used for CSCs evaluation in peripheral blood and EBUS/TBNA aspirates from N1,N2 lymph nodes in lung cancer patients.
Of 30 patients the LNs metastases were confirmed in 18 patients. We noticed presence of PD-L1 on putative lung CSCs- CD133 + EpCAM+ cells. A higher percentage of CD133 + EpCAM+PD-L1+ cells was observed in patients with metastatic in LNs- median value = 4.38% than in patients without LNs metastases- median value = 0,015% (p < 0.05). The highest proportion of PD-L1+ CSCs was found in adenocarcinoma patients and in those with oncogene addiction what indicate an particular biology of this type of lung cancer.
The presence of CSCs with expression of PD-L1 in the metastatic LNs might suggest their immunogenic potential. EBUS/TBNA is commonly used in diagnosis and staging of lung cancer, so the analysis of the cells in metastatic LNs may fit in "immunoscoring" before immunotherapy.
免疫疗法已被发现可有效延长某些肺癌患者的生存期。目前正在寻找新的免疫生物标志物，以选择最适合该疗法的患者。有研究表明，癌症干细胞（CSCs）是肿瘤起始、维持和转移潜能的关键。然而，CSCs 逃避癌症免疫监视的作用尚不清楚。本研究旨在评估转移性肺癌患者淋巴结中 CSCs 的表型，并检测 CSCs 上 PD-L1 的表达。
采用流式细胞术检测肺癌患者外周血和 EBUS/TBNA 抽吸物中 CSCs 的表型。
30 例患者中，18 例患者的淋巴结转移得到证实。我们注意到，在肺 CSCs-CD133+EpCAM+细胞上存在 PD-L1。在有淋巴结转移的患者中，CD133+EpCAM+PD-L1+细胞的比例更高，中位数为 4.38%，而在无淋巴结转移的患者中，中位数为 0.015%（p<0.05）。在腺癌患者和存在致癌基因依赖性的患者中发现了 PD-L1+CSC 的最高比例，这表明了这种类型肺癌的特殊生物学特性。
在转移性淋巴结中存在表达 PD-L1 的 CSCs，可能提示其具有免疫原性。EBUS/TBNA 常用于肺癌的诊断和分期，因此对转移性淋巴结中细胞的分析可能符合免疫治疗前的“免疫评分”。
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