单细胞图谱揭示复发性胶质母细胞瘤中的免疫抑制微环境与Treg细胞景观
Single-cell atlas reveals the immunosuppressive microenvironment and Treg cells landscapes in recurrent Glioblastoma
原文发布日期:2024-03-01
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Patients diagnosed with glioblastoma (GBM) have the most aggressive tumor progression and lethal recurrence. Research on the immune microenvironment landscape of tumor and cerebrospinal fluid (CSF) is limited. At the single-cell level, we aim to reveal the recurrent immune microenvironment of GBM and the potential CSF biomarkers and compare tumor locations. We collected four clinical samples from two patients: malignant samples from one recurrent GBM patient and non-malignant samples from a patient with brain tumor. We performed single-cell RNA sequencing (scRNA-seq) to reveal the immune landscape of recurrent GBM and CSF. T cells were enriched in the malignant tumors, while Treg cells were predominately found in malignant CSF, which indicated an inhibitory microenvironment in recurrent GBM. Moreover, macrophages and neutrophils were significantly enriched in malignant CSF. This indicates that they an important role in GBM progression. S100A9, extensively expressed in malignant CSF, is a promising biomarker for GBM diagnosis and recurrence. Our study reveals GBM’s recurrent immune microenvironment after chemoradiotherapy and compares malignant and non-malignant CSF samples. We provide novel targets and confirm the promise of liquid CSF biopsy for patients with GBM.
被诊断为胶质母细胞瘤(GBM)的患者面临最具侵袭性的肿瘤进展和致命性复发。目前对肿瘤及脑脊液(CSF)免疫微环境的研究仍有限。本研究旨在单细胞层面揭示GBM复发免疫微环境特征、潜在CSF生物标志物,并比较不同肿瘤部位的差异。我们收集了两例患者的四份临床样本:一例来自复发GBM患者的恶性肿瘤样本,另一例来自脑肿瘤患者的非恶性样本。通过单细胞RNA测序(scRNA-seq)技术,我们揭示了复发GBM及其CSF的免疫图谱。研究发现T细胞在恶性肿瘤组织中富集,而调节性T细胞(Treg)主要存在于恶性CSF中,提示复发GBM存在抑制性微环境。此外,巨噬细胞和中性粒细胞在恶性CSF中显著富集,表明它们在GBM进展中起重要作用。S100A9在恶性CSF中广泛表达,是GBM诊断和复发监测的潜在生物标志物。本研究揭示了放化疗后GBM的复发免疫微环境特征,对比了恶性与非恶性CSF样本,为临床治疗提供了新靶点,并证实了CSF液体活检在GBM患者中的应用前景。
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