Department of Respiratory and Critical Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China; Institute of Systems Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China; Suzhou Institute of Systems Medicine, Suzhou, 215123, Jiangsu, China.
Institute of Systems Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China; Suzhou Institute of Systems Medicine, Suzhou, 215123, Jiangsu, China.
Exp Cell Res. 2022 Aug 1;417(1):113212. doi: 10.1016/j.yexcr.2022.113212. Epub 2022 May 17.
Malignant pleural effusions (MPE) are a common terminal pathway for many types of cancer, especially non-small cell lung cancer (NSCLC). However, the phenotype and differentiation status of MPE-infiltrating CD8 T cells have not yet been systematically addressed. In this study, the surface molecules and cytokine secretion of T cells in MPE and peripheral blood (PB) were analyzed using flow cytometry. We found an increased frequency of CD8 T cells in MPE compared to PB among lung cancer patients, of which the effector memory subset (Tem, CCR7 CD45RA) and central memory subset (Tcm, CCR7 CD45RA) were upregulated. MPE-derived Tem and Tcm subsets expressed more PD1 or CD39, and there was a greater population of cells in these subsets that co-expressed them. In addition, Tem and Tcm cells from MPE had higher cytokine production than terminally differentiated effector memory cells (TemRA, CCR7 CD45RA) and naïve cells (Tnaive, CCR7CD45RA). Our results demonstrate that the Tem and Tcm cells in MPE may have advantages in both tumor reactivity and immune functionality. Altogether, these findings help to characterize the phenotype of MPE-derived CD8 T cells in terms of differentiation and tumor reactivity and reveal their potential as a target for immunotherapy.
恶性胸腔积液(MPE)是许多类型癌症(尤其是非小细胞肺癌 [NSCLC])的常见终末途径。然而,MPE 浸润的 CD8 T 细胞的表型和分化状态尚未得到系统研究。在这项研究中,我们使用流式细胞术分析了 MPE 和外周血(PB)中 T 细胞的表面分子和细胞因子分泌。我们发现与肺癌患者的 PB 相比,MPE 中 CD8 T 细胞的频率增加,其中效应记忆亚群(Tem,CCR7 CD45RA)和中央记忆亚群(Tcm,CCR7 CD45RA)上调。MPE 衍生的 Tem 和 Tcm 亚群表达更多的 PD1 或 CD39,并且这些亚群中共同表达它们的细胞数量更多。此外,MPE 中的 Tem 和 Tcm 细胞产生的细胞因子多于终末分化的效应记忆细胞(TemRA,CCR7 CD45RA)和幼稚细胞(Tnaive,CCR7CD45RA)。我们的研究结果表明,MPE 中的 Tem 和 Tcm 细胞在肿瘤反应性和免疫功能方面可能具有优势。总之,这些发现有助于从分化和肿瘤反应性方面表征 MPE 衍生的 CD8 T 细胞的表型,并揭示它们作为免疫治疗靶点的潜力。