La Manna Marco Pio, Di Liberto Diana, Lo Pizzo Marianna, Mohammadnezhad Leila, Shekarkar Azgomi Mojtaba, Salamone Vincenzo, Cancila Valeria, Vacca Davide, Dieli Costanza, Maugeri Rosario, Brunasso Lara, Iacopino Domenico Gerardo, Dieli Francesco, Caccamo Nadia
Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), University of Palermo, 90129 Palermo, Italy.
Department of Biomedicine Neurosciences and Advanced Diagnostics, School of Medicine, University of Palermo, 90127 Palermo, Italy.
Biomedicines. 2022 Oct 1;10(10):2454. doi: 10.3390/biomedicines10102454.
Glial tumors alone account for 40% of all CNS tumors and present a low survival rate. The tumor microenvironment is a critical regulator of tumor progression and therapeutic effectiveness in glioma. Growing evidence from numerous studies of human solid tumor-infiltrating CD8 T cells indicates that tissue-resident memory T cells (TRM) represent a substantial subpopulation of tumor-infiltrating lymphocytes (TILs). Although it is reported that some types of cancer patients with high immune infiltration tend to have better outcomes than patients with low immune infiltration, it seems this does not happen in gliomas. This study aimed to characterize TRMs cells in the glioma tumor microenvironment to identify their potential predictive and prognostic role and the possible therapeutic applications. Fluorescence activated cell sorting (FACS) analysis and immunofluorescence staining highlighted a statistically significant increase in CD8 TRM cells (CD103 and CD69 CD8 T cells) in gliomas compared to control samples (meningioma). In-silico analysis of a dataset of = 153 stage IV glioma patients confirmed our data. Moreover, the gene expression analysis showed an increase in the expression of TRM-related genes in tumor tissues compared to normal tissues. This analysis also highlighted the positive correlation between genes associated with CD8 TRM and TILs, indicating that CD8 TRMs cells are present among the infiltrating T cells. Finally, high expression of Integrin subunit alpha E (ITGAE), the gene coding for the integrin CD103, and high CD8 TILs abundance were associated with more prolonged survival, whereas high ITGAE expression but low CD8 TILs abundance were associated with lower survival.
仅神经胶质瘤就占所有中枢神经系统肿瘤的40%，且生存率较低。肿瘤微环境是胶质瘤肿瘤进展和治疗效果的关键调节因子。来自众多关于人类实体瘤浸润性CD8 T细胞研究的越来越多的证据表明，组织驻留记忆T细胞（TRM）是肿瘤浸润淋巴细胞（TIL）的一个重要亚群。尽管有报道称，一些免疫浸润高的癌症患者往往比免疫浸润低的患者预后更好，但在胶质瘤中似乎并非如此。本研究旨在对胶质瘤肿瘤微环境中的TRM细胞进行表征，以确定它们潜在的预测和预后作用以及可能的治疗应用。荧光激活细胞分选（FACS）分析和免疫荧光染色显示，与对照样本（脑膜瘤）相比，胶质瘤中CD8 TRM细胞（CD103和CD69 CD8 T细胞）有统计学意义的增加。对153例IV期胶质瘤患者数据集的电子分析证实了我们的数据。此外，基因表达分析表明，与正常组织相比，肿瘤组织中TRM相关基因的表达增加。该分析还突出了与CD8 TRM和TIL相关基因之间的正相关，表明CD8 TRM细胞存在于浸润性T细胞中。最后，整合素亚基α E（ITGAE）（编码整合素CD103的基因）的高表达和高CD8 TIL丰度与更长的生存期相关，而高ITGAE表达但低CD8 TIL丰度与较低的生存期相关。
