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Exploitation of gamma delta T cells in cancer immunotherapy as combined antigen-presenters and cancer cell killers

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The human Vγ9Vδ2 T cells are a unique T cell type, and recent studies of the biology of Vγ9Vδ2 T cells emphasize the potential exploitation of these cells in immunotherapy of cancer. Vγ9Vδ2 T cells exhibit dual functionality in that they are both antigen-presenting cells and cytotoxic towards cancer cells. We have been able to show that Vγ9Vδ2 T cells can kill cancer cells from various cancer types such as breast cancer, leukemia cancer lines and malignant melanoma, with a significantly increased killing upon treatment of the cancer cells with Zoledronic acid. In addition, cross presentation of antigens was also confirmed by using flow cytometry and chromium release assays. Furthermore, Vγ9Vδ2 T cells were also able to induce a conventional CMV-specific αβ-T cells response/culture. Unique to these findings is that it is the same γδ T cells that exhibit both functionality as APC and cancer killers. This combined with the ease of expanding Vγ9Vδ2 T cells in vitro to billions of cells, makes Vγ9Vδ2 T cells an attractive alternative to conventional antigen-presenting cells, such as dendritic cells. Moreover, a cell that kills tumor targets and concurrently induces a response against the tumor cell it kills, holds great potential for clinical use. We are currently setting up in vivo experiments using the NOG mouse model to study the in vivo capacity of Vγ9Vδ2 T cells to delay tumor growth.

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Correspondence to Gitte Holmen Olofsson.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Keywords

  • Breast Cancer
  • Malignant Melanoma
  • Zoledronic Acid
  • Cancer Immunotherapy
  • Cancer Line