Single-cell transcriptome reveals features of immune environment and mechanisms of immune escape in giant cell tumor of bone
10.3760/cma.j.cn121113-20220821-00461
- VernacularTitle:应用单细胞测序转录组分析骨巨细胞瘤的免疫环境特征及免疫逃逸机制
- Author:
Zhiwu REN
1
;
Chao ZHANG
;
Junyang LIU
;
Yue XIE
;
Zhichao LIAO
;
Ting LI
;
Xinyue LIU
;
Ruwei XING
;
Jianmin SONG
;
Jilong YANG
Author Information
1. 天津医科大学肿瘤医院骨与软组织肿瘤科，国家恶性肿瘤临床医学研究中心，天津市恶性肿瘤临床医学研究中心，天津市肿瘤分子流行病重点实验室，天津 300060
- Keywords:
Giant cell tumor of bone;
Single-cell analysis;
CD8-positive T-lymphocytes;
Tumor escape
- From:
Chinese Journal of Orthopaedics
2022;42(21):1441-1449
- CountryChina
- Language:Chinese
-
Abstract:
Objective:This study aims to reveal the special immune infiltrating environment and possible immune escape mechanism of giant cell tumor of bone through single-cell sequencing data.Methods:The fresh samples obtained from 4 patients with primary giant cell tumor of bone from January 2018 to December 2021 were collected, and single-cell transcriptome sequencing was performed on the 10X platform to explore the characteristics and immune environment of giant cell tumor of bone by using t-distributed stochastic neighbor embedding ( t-SNE). The main cell types and signal pathways of immune cell regulation and function in giant cell tumor of bone were observed by cell communication analysis. Results:Cell clustering, the definition of basic cell types, the classification of immune cells, and the mutual regulatory relationship between cell types were analyzed for 35 643 single-cell data from 4 giant cell tumor samples of bone. It was found that giant cell tumor of bone was composed of 9 basic cell types, in which the immune cells were mainly CD8 + T cells (51%) and the non-immune cells were mainly fibroblast like spindle stromal cells (74%). The immune infiltration of giant cell tumor of bone is dominated by cytotoxic CD8 + T cells and lacks exhausted CD8 + T cells. CD4 + T cells are characterized by high expression of immune checkpoint genes CTLA4 and TIGIT. In giant cell tumor of bone, immune cells mainly act on multinucleated osteoclast like giant cells through PARs and CCL signaling pathways, but not stromal cells. Conclusion:This study defined the main cell types of giant cell tumor of bone through single cell sequencing data, and further revealed the composition characteristics of its immune infiltration, and found that the target of its immune cells was mainly multinuclear osteoclast like giant cells, which provided effective information for further understanding the occurrence and development of giant cell tumor of bone.
