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High-dimensional single-cell analysis unveils distinct immune signatures of peripheral blood in patients with pancreatic ductal adenocarcinoma.
Pan, Yu; Gao, Jianfeng; Lin, Jiajing; Ma, Yuan; Hou, Zelin; Lin, Yali; Wen, Shi; Pan, Minggui; Lu, Fengchun; Huang, Heguang.
Afiliação
  • Pan Y; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
  • Gao J; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
  • Lin J; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
  • Ma Y; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
  • Hou Z; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
  • Lin Y; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
  • Wen S; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
  • Pan M; Department of Oncology and Hematology and Division of Research, Kaiser Permanente, Santa Clara, CA, United States.
  • Lu F; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
  • Huang H; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
Front Endocrinol (Lausanne) ; 14: 1181538, 2023.
Article em En | MEDLINE | ID: mdl-37347110
Introduction: Pancreatic 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. Methods: We 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. Results: We 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. Conclusion: Our RNA-seq and proteomic results provide valuable insight for understanding the immune cell composition of peripheral blood of patients with PDAC.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático Idioma: En Ano de publicação: 2023 Tipo de documento: Article