IL-33-expanded human Vγ9Vδ2 T cells have anti-lymphoma effect in a mouse tumor model

Eur J Immunol. 2017 Dec;47(12):2137-2141. doi: 10.1002/eji.201747093. Epub 2017 Sep 29.

Abstract

From several years, the anticancer effects of Vγ9 T lymphocytes make these cells good candidates for cancer immunotherapies. However, the proved efficacy of γδ Τ cell-based cancer immunotherapies in some clinical trials was minimized due to the inherent toxicity of IL-2, which is essential for the combination therapy with Phosphoantigen (PAg). Recently, we showed that IL-33, a γ chain receptor-independent cytokine, was able to induce the in vitro proliferation of PAg-activated Vγ9 T cells, which were fully functional expressing IFN-γ and TNF-α and showing in vitro anti-tumor cytotoxicity. We proposed IL-33 as an alternative to IL-2 for Vγ9 T cell-based cancer immunotherapies, and have therefore evaluated the efficacy of this cytokine in preclinical investigations. This study shows that human Vγ9 T cells are able to proliferate in a mouse model with the combination of PAg and rhIL-33, and that IL-33-expanded Vγ9 T cells can prevent tumor growth in a mouse lymphoma model.

Keywords: Cancer; IL-33; Immunotherapy; Lymphoma; Phosphoantigens; Vγ9Vδ2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cells, Cultured
  • Humans
  • Immunotherapy / methods*
  • Interleukin-33 / genetics
  • Interleukin-33 / pharmacology*
  • Lymphoma / drug therapy*
  • Lymphoma / immunology
  • Lymphoma / metabolism
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • Recombinant Proteins / pharmacology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation*
  • Tumor Burden / drug effects
  • Tumor Burden / immunology
  • Xenograft Model Antitumor Assays / methods*

Substances

  • IL33 protein, human
  • Interleukin-33
  • Receptors, Antigen, T-Cell, gamma-delta
  • Recombinant Proteins