Department of Pathology, Medical University of Warsaw, Pawinskiego 7 Street, 02-106, Warsaw, Poland.
Department of Pulmonary Medicine, Erasmus MC Cancer Institute, s-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
Cancer Immunol Immunother. 2021 Feb;70(2):453-461. doi: 10.1007/s00262-020-02648-y. Epub 2020 Aug 17.
Cancer stem cells (CSCs) are implicated in tumor initiation and development of metastasis. However, whether CSCs also affect the immune system is not fully understood. We investigated correlations between the PD-L1 CSCs, changes in T-cell phenotype in metastatic and non-metastatic lymph nodes (LNs) and response to treatment.
LNs' aspirates were obtained during the EBUS/TBNA procedure of 20 NSCLC patients at different stages of the disease. CSCs and T-cell characteristics were determined by flow cytometry.
PD-L1 CSCs positively correlated with the percentage of Tregs, PD-1 CD4 T cells and Tim3 CD4 T cells, whereas PD-L1 CSCs were negatively correlated with CD4 T cells and CD28 CD4 T cells. The percentage of PD-L1 CSCs was higher in patients with progressive disease (PD) as compared to patients with stable disease (SD) or partial response (PR). Among T cells, only PD-1 CD4 T cells and Tim3 CD4 T-cell frequencies were higher in patients with PD as compared to patients with SD or PR.
The frequency of PD-L1 CSCs associates with an altered T-cell frequency and phenotype indicating that CSCs can affect the immune system. The higher percentage of PD-L1 CSCs in patients with PD may confirm their resistance to conventional therapy, suggesting that CSCs may be an interesting target for immunotherapy.
癌症干细胞（CSCs）被认为与肿瘤的发生和转移有关。然而，CSCs 是否也会影响免疫系统还不完全清楚。我们研究了 PD-L1 CSCs 与转移性和非转移性淋巴结（LNs）中 T 细胞表型的变化以及对治疗的反应之间的相关性。
在 20 名 NSCLC 患者疾病的不同阶段，通过 EBUS/TBNA 程序获得 LNs 抽吸物。通过流式细胞术确定 CSCs 和 T 细胞特征。
PD-L1 CSCs 与 Treg、PD-1 CD4 T 细胞和 Tim3 CD4 T 细胞的百分比呈正相关，而与 CD4 T 细胞和 CD28 CD4 T 细胞呈负相关。进展性疾病（PD）患者的 PD-L1 CSCs 百分比高于稳定疾病（SD）或部分缓解（PR）患者。在 T 细胞中，只有 PD-1 CD4 T 细胞和 Tim3 CD4 T 细胞的频率在 PD 患者中高于 SD 或 PR 患者。
PD-L1 CSCs 的频率与改变的 T 细胞频率和表型相关，表明 CSCs 可以影响免疫系统。PD 患者中 PD-L1 CSCs 的百分比较高可能证实了他们对常规治疗的耐药性，这表明 CSCs 可能是免疫治疗的一个有趣靶点。
