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Oncoscience. 2015 May 15;2(5):476-82. eCollection 2015.

Rapid and efficient transfer of the T cell aging marker CD57 from glioblastoma stem cells to CAR T cells.

Author information

1
Department of Radiation Oncology, University Hospital Freiburg, Freiburg, Germany ; German Cancer Consortium (DKTK), Freiburg, and German Cancer Research Center (DKFZ), Heidelberg, Germany.

Abstract

Adoptive transfer of T cells expressing chimeric antigen receptors (CARs) holds great promise for cancer treatment. We recently developed CAR T cells targeting the prototypic cancer stem cell marker AC133 and showed that these CAR T cells killed AC133+ glioblastoma stem cells (GBM-SCs) in vitro and inhibited the growth of brain tumors initiated from GBM-SCs in xenograft mouse models in vivo . Upon coincubation with GBM-SCs, we observed strong upregulation of the T cell aging marker CD57, but other phenotypical or functional changes usually associated with terminal T cell differentiation could not immediately be detected. Here, we provide evidence suggesting that CD57 is rapidly and efficiently transferred from CD57+ GBM-SCs to preactivated T cells and that the transfer is greatly enhanced by specific CAR/ligand interaction. After separation from CD57+ tumor cells, CD57 epitope expression on T cells decreased only slowly over several days. We conclude that CD57 transfer from tumor cells to T cells may occur in patients with CD57+ tumors and that it may have to be considered in the interpretation of phenotyping results for tumor-infiltrating lymphocytes and perhaps also in the characterization of tumor-specific T cells from tumor or lymph node homogenates or peripheral blood mononuclear cells.

KEYWORDS:

CD57; cancer stem cells; chimeric antigen receptor; glioblastoma; trogocytosis

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