High-dimensional single-cell analysis unveils distinct immune signatures of peripheral blood in patients with pancreatic ductal adenocarcinoma

Frontiers in Endocrinology

Endocrinology

Jianfeng Gao¹  Fengchun Lu¹  Yu Pan¹  Yali Lin¹  Jiajing Lin¹  Yuan Ma¹  Shi Wen¹  Heguang Huang¹  Zelin Hou¹  Minggui Pan² 

[1] Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China;Department of Oncology and Hematology and Division of Research, Kaiser Permanente, Santa Clara, CA, United States;

关键词: pancreatic ductal adenocarcinoma;    single-cell sequencing;    T-cell receptor immune signatures;    tumor;    signatures calculation;   

DOI  :  10.3389/fendo.2023.1181538

 received in 2023-03-07, accepted in 2023-05-09,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with poor response to immune checkpoint inhibitors. The mechanism of such poor response is not completely understood.MethodsWe assessed T-cell receptor (TCR) repertoire and RNA expression at the single-cell level using high-dimensional sequencing of peripheral blood immune cells isolated from PDAC patients and from healthy human controls. We validated RNA-sequencing data by performing mass cytometry (CyTOF) and by measuring serum levels of multiple immune checkpoint proteins.ResultsWe found that proportions of T cells (CD45+CD3+) were decreased in PDAC patients compared to healthy controls, while proportion of myeloid cells was increased. The proportion of cytotoxic CD8+ T cells and the level of cytotoxicity per cell were increased in PDAC patients, with reduced TCR clonal diversity. We also found a significantly enriched S100A9+ monocyte population and an increased level of TIM-3 expression in immune cells of peripheral blood in PDAC patients. In addition, the serum level of soluble TIM-3 (sTIM-3) was significantly higher in PDAC patients compared to the non-PDAC participants and correlated with worse survival in two independent PDAC cohorts. Moreover, sTIM-3 exhibited a valuable role in diagnosis of PDAC, with sensitivity and specificity of about 80% in the training and validation groups, respectively. We further established an integrated model by combining sTIM-3 and carbohydrate antigen 19- 9 (CA19-9), which had an area under the curve of 0.974 and 0.992 in training and validation cohorts, respectively.ConclusionOur RNA-seq and proteomic results provide valuable insight for understanding the immune cell composition of peripheral blood of patients with PDAC.

【 授权许可】

Unknown   
Copyright © 2023 Pan, Gao, Lin, Ma, Hou, Lin, Wen, Pan, Lu and Huang