Wang Xingdong, Ge Yizhi, Hou Yuting, Wang Xiaodong, Yan Zhengcun, Li Yuping, Dong Lun, She Lei, Tang Can, Wei Min, Zhang Hengzhu
Department of Neurosurgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University/Clinical medical college, Yangzhou University, Yangzhou, Jiangsu, 225000, China.
Department of Radiation Oncology, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210009, China.
Cancer Gene Ther. 2024 May;31(5):790-801. doi: 10.1038/s41417-024-00740-4. Epub 2024 Mar 1.
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）的患者具有最具侵袭性的肿瘤进展和致命的复发情况。关于肿瘤和脑脊液（CSF）免疫微环境格局的研究有限。在单细胞水平上，我们旨在揭示GBM的复发性免疫微环境和潜在的脑脊液生物标志物，并比较肿瘤位置。我们从两名患者身上收集了四个临床样本：一名复发性GBM患者的恶性样本和一名脑肿瘤患者的非恶性样本。我们进行了单细胞RNA测序（scRNA-seq）以揭示复发性GBM和脑脊液的免疫格局。T细胞在恶性肿瘤中富集，而调节性T细胞主要存在于恶性脑脊液中，这表明复发性GBM中存在抑制性微环境。此外，巨噬细胞和中性粒细胞在恶性脑脊液中显著富集。这表明它们在GBM进展中起重要作用。在恶性脑脊液中广泛表达的S100A9是GBM诊断和复发的一个有前景的生物标志物。我们的研究揭示了放化疗后GBM的复发性免疫微环境，并比较了恶性和非恶性脑脊液样本。我们提供了新的靶点，并证实了脑脊液液体活检对GBM患者的前景。
