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Innate Anti-breast Cancer Immunity of Apoptosis-resistant Human γδ-T cells

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Summary

We previously identified a CD2-initiated signaling pathway which inhibits activation-induced cell death in mitogen-stimulated human γδ-T cells permitting the large-scale expansion of these cells. Here we report the innate anti-tumor activity of expanded human γδ-T cells against human breast cancer cells. Apoptosis-resistant human γδ-T cells which were expanded in vitro from cultured human peripheral blood mononuclear cells displayed lytic activity against breast cancer cell lines MDA-MB-231, MCF-7 and T-47D, but failed to kill normal human skin fibroblasts and normal human liver cells. Monoclonal antibodies (mAb) directed against the γδ-T cell receptor (TCR) or mAb directed against either the Vγ9 or the Vδ2 TCR chains were able to block γδ-T cell-mediated lysis of MDA-MB-231 cells. In addition, mAb against intercellular adhesion molecules-1 (ICAM-1/CD54) or CD18 (β subunit of ICAM-1 counter–receptor) also blocked γδ-T cell-mediated killing of MDA-MB-231 cells. Ex vivo expanded human γδ-T cells are thus able to innately recognize and kill human breast cancer cells in a γδ-TCR-dependent manner; ICAM-1 and CD18 also appear to be involved in the interactions between sensitive breast cancer cells and cytolytic γδ-T cells. As apoptosis-resistant human γδ-T cells can now readily be expanded to large numbers (clinical scale), these findings must be considered in the context of developing adoptive immunotherapy strategies to exploit γδ-T cell innate immune responses for the primary or adjuvant treatment of breast cancer.

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  1. Bone Marrow Transplantation Program, University of Alabama at Birmingham, Birmingham, AL, USA

    Ben L. Guo, Zhiyong Liu, Wayne A. Aldrich & Richard D. Lopez

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  1. Ben L. Guo
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  2. Zhiyong Liu
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  3. Wayne A. Aldrich
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  4. Richard D. Lopez
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Correspondence to Richard D. Lopez.

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Guo, B.L., Liu, Z., Aldrich, W.A. et al. Innate Anti-breast Cancer Immunity of Apoptosis-resistant Human γδ-T cells. Breast Cancer Res Treat 93, 169–175 (2005). https://doi.org/10.1007/s10549-005-4792-8

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