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Exosomes derived from exhausted CD8+ T cells impaired the anticancer function of normal CD8+ T cells
  1. Xiaochen Wang1,
  2. Haiyuan Shen1,
  3. Qifeng He1,
  4. Wenfang Tian2,
  5. Anliang Xia1,
  6. Xiao-Jie Lu1
  1. 1 Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
  2. 2 Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
  1. Correspondence to Dr Xiao-Jie Lu, Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; 189{at}whu.edu.cn

Abstract

Background Previous studies suggested that diverse cells in cancer microenvironment can interact with CD8+ T cells via exosomes. We designed this study to explore the potential interaction between exhausted CD8+ T cells and normal CD8+ T cells via exosome.

Methods Fluorescence activated cell sorting was used to get PD1+TIM3+/PD1−TIM3−CD8+ T cells. Exosomes from the cell culture medium were collected by ultracentrifugation. Microarrays were performed to analyse the lncRNA expression profile in exosomes.

Results Functional exhausted CD8+ T cells could secrete vast exosomes, which can be uptake by normal CD8+ T cells, and impaired their proliferation (Ki67), cell activity (CD69) and the production of cytokines such as interferon-γ and interleukin-2. Microarray detection identified 257 candidate lncRNAs differently expressed in exosomes derived from exhausted CD8+ T cells and non-exhausted CD8+ T cells. Functional enrichment analysis indicated that these lncRNAs actively participated in the regulation of diverse process of CD8+ T cell activity, like metabolism, gene expression, biosynthetic process and so forth.

Conclusions The exosomes derived from exhausted CD8+ T cells could be uptake by non-exhausted CD8+ T cells and subsequently impaired the function of receipt cells. Exosomes secreted from exhausted CD8+ T cells have distinct lncRNA expression profiles which are significantly different from those in exosomes secreted by non-exhausted CD8+ T cells.

  • CD8+ T Cells
  • T cell exhaustion
  • exosome
  • lncRNA

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Footnotes

  • XW, HS and QH contributed equally.

  • Contributors Conception and design: XJL. Provision of study materials or patients: XW, QH and HS. Collection and assembly of data: XJL, WT and HS. Data analysis and interpretation: XW and QH. Manuscript writing: XJL and XW. Manuscript revision: XW, QH, HS and AX. Final approval of manuscript: all authors.

  • Funding This work was supported by the National Natural Science Foundation (Grant No: 81772596 to XJL); and the Postgraduate Education Reform Project of Jiangsu Province (Grant No: JX22013394 to XW).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Approved by the First Affiliated Hospital of Nanjing Medical University.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Correction notice This article has been corrected since it was published Online First. Figure 1 has been replaced by the correct version.

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