Single-Cell Atlas Reveals Complexity of the Immunosuppressive Microenvironment of Initial and Recurrent Glioblastoma

Frontiers in Immunology

Hao Li¹  Weilun Fu¹  Ran Huo¹  Jiangfei Wang¹  Yuming Jiao¹  Yong Cao¹  Jie Wang¹  Jizong Zhao¹  Shuo Wang¹  Zihan Yan¹  Dexi Chen³  Wenjing Wang³ 

[1] China National Clinical Research Center for Neurological Diseases, Beijing, China;Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China;Institute of Hepatology, Capital Medical University Affiliated Beijing You’an Hospital, Beijing, China;

关键词: glioblastoma;    recurrent glioblastoma;    CyTOF;    immune profiling;    microenvironment;   

DOI  :  10.3389/fimmu.2020.00835

来源: DOAJ

【 摘 要 】

The Glioblastoma (GBM) immune microenvironment plays a critical role in tumor development, progression, and prognosis. A comprehensive understanding of the intricate milieu and its interactions remains unclear, and single-cell analysis is crucially needed. Leveraging mass cytometry (CyTOF), we analyzed immunocytes from 13 initial and three recurrent GBM samples and their matched peripheral blood mononuclear cells (pPBMCs). Using a panel of 30 markers, we provide a high-dimensional view of the complex GBM immune microenvironment. Hematoxylin and eosin staining and polychromatic immunofluorescence were used for verification of the key findings. In the initial and recurrent GBMs, glioma-associated microglia/macrophages (GAMs) constituted 59.05 and 27.87% of the immunocytes, respectively; programmed cell death-ligand 1 (PD-L1), T cell immunoglobulin domain and mucin domain-3 (TIM-3), lymphocyte activation gene-3 (LAG-3), interleukin-10 (IL-10) and transforming growth factor-β (TGFβ) demonstrated different expression levels in the GAMs among the patients. GAMs could be subdivided into different subgroups with different phenotypes. Both the exhausted T cell and regulatory T (Treg) cell percentages were significantly higher in tumors than in pPBMCs. The natural killer (NK) cells that infiltrated into the tumor lesions expressed higher levels of CXC chemokine receptor 3 (CXCR3), as these cells expressed lower levels of interferon-γ (IFNγ). The immune microenvironment in the initial and recurrent GBMs displayed similar suppressive changes. Our study confirmed that GAMs, as the dominant infiltrating immunocytes, present great inter- and intra-tumoral heterogeneity and that GAMs, increased exhausted T cells, infiltrating Tregs, and nonfunctional NK cells contribute to local immune suppressive characteristics. Recurrent GBMs share similar immune signatures with the initial GBMs except the proportion of GAMs decreases.

【 授权许可】

Unknown