细胞毒性T细胞
CD8型
肿瘤微环境
CX3CR1型
生物
表型
T细胞
免疫学
癌症研究
小胶质细胞
肿瘤进展
胶质瘤
免疫系统
炎症
趋化因子
体外
基因
癌症
生物化学
趋化因子受体
遗传学
作者
Philip Schmassmann,Julien Roux,Steffen Dettling,Sabrina A. Hogan,Tala Shekarian,Tomás A. Martins,Marie‐Françoise Ritz,Sylvia Herter,Marina Bacac,Gregor Hütter
标识
DOI:10.1101/2022.06.17.496574
摘要
Abstract Glioblastoma (GBM) harbors a highly immunosuppressive tumor microenvironment (TME) which influences glioma growth. Major efforts have been undertaken to describe the TME on a single-cell level. However, human data on regional differences within the TME remain scarce. Here, we performed high-depth single-cell RNA sequencing (scRNAseq) on paired biopsies from the tumor center, peripheral infiltration zone and blood of five primary GBM patients. Through analysis of > 45’000 cells, we revealed a regionally distinct transcription profile of microglia (MG) and monocyte-derived macrophages (MdMs) and an impaired activation signature in the tumor-peripheral cytotoxic-cell compartment. Comparing tumor-infiltrating CD8 + T cells with circulating cells identified CX3CR1 high and CX3CR1 int CD8 + T cells with effector and memory phenotype, respectively, enriched in blood but absent in the TME. Tumor CD8 + T cells displayed a tissue-resident memory phenotype with dysfunctional features. Our analysis provides a regionally resolved mapping of transcriptional states in GBM-associated leukocytes, serving as an additional asset in the effort towards novel therapeutic strategies to combat this fatal disease.
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