Irradiation enhances human T-cell function by upregulating CD70 expression on antigen-presenting cells in vitro

Jianping Huang, Qiong J. Wang, Shicheng Yang, Yong F. Li, Mona El-Gamil, Steven A. Rosenberg, Paul F. Robbins

Research output: Contribution to journalArticle

Abstract

In addition to the direct killing of tumor cells, radiation therapy can alter the balance of immune cells in vivo due to the differential radiosensitivity of different cell types. The addition of adjuvant radiation therapy before adoptive cell transfer therapy has been shown to enhance antitumor responses in both mouse models and clinical trials. This study examines the effects of in vitro irradiation on the phenotype and function of human antigen-presenting cells. The results indicated that irradiation upregulated CD70 expression on both B cells and mature dendritic cells (DCs). Expression of CD70 on mature DCs was enhanced in a dose-dependent manner, whereas under the same conditions, no significant upregulation of CD80, CD86, or CD40 was observed. The levels of expression of CD70 induced on mature DC by irradiation correlated highly with the ability of those cells to stimulate T-cell proliferation and interferon-γ production. Furthermore, significant reductions in T-cell proliferation and interferon-γ production were seen when CD70 expression on DCs was partially reduced using shRNA, as well as when DCs were incubated with a blocking anti-CD70 antibody. Radiation therapy may therefore enhance T-cell activation in vivo through the CD27 pathway by virtue of its ability to upregulate the expression of CD70 on antigen-presenting cells.

Original languageEnglish (US)
Pages (from-to)327-335
Number of pages9
JournalJournal of Immunotherapy
Volume34
Issue number4
DOIs
StatePublished - May 1 2011

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Keywords

  • CD27
  • CD70
  • adoptive cell transfer
  • cancer immunotherapy
  • costimulation
  • human T cells
  • mature human dendritic cells
  • radiation
  • total body irradiation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

Cite this

Huang, J., Wang, Q. J., Yang, S., Li, Y. F., El-Gamil, M., Rosenberg, S. A., & Robbins, P. F. (2011). Irradiation enhances human T-cell function by upregulating CD70 expression on antigen-presenting cells in vitro. Journal of Immunotherapy, 34(4), 327-335. https://doi.org/10.1097/CJI.0b013e318216983d