Kwiecien Iwona, Skirecki Tomasz, Polubiec-Kownacka Małgorzata, Raniszewska Agata, Domagala-Kulawik Joanna
Department of Internal Medicine and Hematology Laboratory of Flow Cytometry, Military Medical Institute, Warsaw, ul. Szaserow 128, 04-141 Warsaw, Poland.
Laboratory of Flow Cytometry, Centre of Postgraduate Medical Education, ul. Marymoncka 99/103, 01-813 Warsaw, Poland.
Cancers (Basel). 2019 Apr 21;11(4):567. doi: 10.3390/cancers11040567.
The overexpression of programmed death-1 (PD-1) and cytotoxic T cell antigen 4 (CTLA-4) receptors on T cells are among the major mechanisms of tumor immunoevasion. However, the expression pattern of these receptors on T cell subpopulations of a different activation status and at different sites is poorly characterized. Thus, we analyzed the expression of PD-1 and CTLA-4 on the naïve, activated, memory, and activated memory T cells. Bronchoalveolar lavage fluid (BALF) from the lung affected by lung cancer (clBALF), the opposite 'healthy' lung (hlBALF), and peripheral blood (PB) samples were collected from 32 patients. The cells were analyzed by multiparameter flow cytometry. The proportion of memory, activated, and activated memory CD8+ cells with the expression of PD-1 and CTLA-4 were elevated in the clBALF when compared to the hlBALF (insignificantly), but these proportions were significantly higher in the BALF when compared with the PB. The proportions of PD-1+ and CTLA-4+ T cells were elevated in the squamous cell carcinoma when compared to the adenocarcinoma patients. Also, the expression of PD-1 and CTLA-4 on T cells from the BALF was significantly higher than from PB. We report for the first time the differential expression of checkpoint molecules on CD4+ and CD8+ lymphocytes at a different stage of activation in the local environment of lung cancer. Moreover, the circulating T cells have a distinct expression of these receptors, which suggests their poor utility as biomarkers for immunotherapy.
程序性死亡-1（PD-1）和细胞毒性T细胞抗原4（CTLA-4）受体在T细胞上的过表达是肿瘤免疫逃逸的主要机制之一。然而，这些受体在不同激活状态和不同部位的T细胞亚群上的表达模式却鲜有描述。因此，我们分析了PD-1和CTLA-4在初始、活化、记忆和活化记忆T细胞上的表达情况。收集了32例患者受肺癌影响的肺组织的支气管肺泡灌洗液（clBALF）、对侧“健康”肺组织的支气管肺泡灌洗液（hlBALF）以及外周血（PB）样本。通过多参数流式细胞术对细胞进行分析。与hlBALF相比，clBALF中表达PD-1和CTLA-4的记忆、活化和活化记忆CD8+细胞比例升高（不显著），但与PB相比，这些比例在BALF中显著更高。与腺癌患者相比，鳞状细胞癌患者中PD-1+和CTLA-4+ T细胞的比例升高。此外，BALF中T细胞上PD-1和CTLA-4的表达显著高于PB中的T细胞。我们首次报道了在肺癌局部环境中不同激活阶段CD4+和CD8+淋巴细胞上检查点分子的差异表达。此外，循环T细胞对这些受体有独特的表达，这表明它们作为免疫治疗生物标志物的效用不佳。
