CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The Abundance of Tumor-Infiltrating CD8(+) Tissue Resident Memory T Lymphocytes Correlates with Patient Survival in Glioblastoma.
The Abundance of Tumor-Infiltrating CD8(+) Tissue Resident Memory T Lymphocytes Correlates with Patient Survival in Glioblastoma.
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胶质瘤单独就占所有中枢神经系统肿瘤的40%,且生存率低。肿瘤微环境是胶质瘤进展和治疗效果的关键调节因素。来自大量人类实体瘤浸润性CD8+ T细胞研究的越来越多证据表明,组织驻留记忆T细胞(TRM)是TIL(肿瘤浸润淋巴细胞)(TILs)的一个重要亚群。尽管有报道称某些类型的癌症患者中免疫浸润高者往往比免疫浸润低者预后更好,但这种情况似乎并未在胶质瘤中出现。
本研究旨在表征胶质瘤肿瘤微环境中的TRM细胞,以确定其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突出显示,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)有统计学显著增加。对n = 153例IV期胶质瘤患者数据集的计算机分析证实了我们的数据。
此外,基因表达分析显示,与正常组织相比,肿瘤组织中TRM相关基因的表达增加。该分析还强调了与CD8+ TRM相关的基因和TILs之间的正相关,表明CD8+ TRM细胞存在于浸润的T细胞中。
最后,整合素亚基αE(ITGAE,编码整合素CD103的基因)高表达和CD8+ TILs高丰度与更长的生存期相关,而ITGAE高表达但CD8+ TILs低丰度则与较低的生存期相关。
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 n = 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.
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