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Expansion of Th1-like Vγ9Vδ2T cells by new-generation IMiDs, lenalidomide and pomalidomide, in combination with zoledronic acid

Leukemia volume 31, pages 258–262 (2017)Cite this article

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Multiple myeloma (MM) still remains incurable even with the implementation of novel therapeutic modalities, leading to the idea to develop various forms of immunotherapies. One such approach is the application of γδ T cells. Similar to NK cells, γδ T cells are important effectors in the first-line defense against infections and tumors, and have a critical role in host defense and tumor surveillance.1, 2, 3 In human, γδ T cells are divided into two predominant subpopulations by T-cell receptor V gene usage, namely Vδ1 γδT cells and Vγ9Vδ2 γδ T (γδ2 T) cells. γδ2 T cells represent a majority of γδ T cells in peripheral blood and bone marrow in human. Cancer cells, including MM cells, are generally accepted to over-express cognate antigens and/or ligands for γδ2 T cells, including phosphoantigens such as isopentenyl pyrophosphate, an intermediate of the mevalonate pathway, and stress proteins such as heat shock proteins. Thus, γδ2 T cells are surmised to selectively recognize and kill malignant cells while sparing healthy bystander cells.

Human γδ2 T cells have been demonstrated to be expanded ex vivo by aminobisphosphonates in combination with interleukin (IL)-2, and effectively target and impair MM cells.4, 5 We previously reported that γδ2T cells are robustly expanded with zoledronic acid (Zol) and IL-2 from peripheral blood mononuclear cells (PBMCs) and exert marked cytotoxic activity against MM cells and osteoclasts.6 Besides, γδ2T cells are capable of MHC-independent killing of target cells.7, 8 Therefore, γδ2 T cells expanded ex vivo have attracted attention as potent effectors available to immunotherapy against MM. For clinical application of immunotherapy with γδ2 T cells, we need to not only improve efficiency of ex vivo expansion and activation of γδ2 T cells but also maintain and potentiate their antitumor activity in vivo after infusion to patients with malignancies.

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Acknowledgements

This work was supported in part by Grant-in-Aid for Young Scientists (B) to HM, RA and SN, Grants-in-aid for Scientific Research (C) to MA, and a Grant-in-aid for Cancer Research (17–16) to MA from the Ministry of Health, Labor and Welfare of Japan. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

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Author notes

  1. T Harada and H Miki: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School, Tokushima, Japan

    T Harada, Q Cui, A Oda, A Bat-Erdene, K Sogabe, M Iwasa, S Fujii, S Nakamura, K Kagawa, S Yoshida, I Endo, K Aihara & M Abe

  2. Division of Transfusion Medicine and Cell Therapy, Tokushima University Hospital, Tokushima, Japan

    H Miki

  3. Department of Orthodontics and Dentofacial Orthopedics, The University of Tokushima Graduate School of Oral Science, Tokushima, Japan

    R Amachi

  4. Department of Histology and Oral Histology, The University of Tokushima Graduate School of Oral Science, Tokushima, Japan

    J Teramachi

  5. Department of Hematology, Tokushima Prefectural Central Hospital, Tokushima, Japan

    S Ozaki

  6. Fujii Memorial Institute of Medical Sciences, Tokushima University, Tokushima, Japan

    T Matsumoto

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  1. T Harada
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Correspondence to M Abe.

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Harada, T., Miki, H., Cui, Q. et al. Expansion of Th1-like Vγ9Vδ2T cells by new-generation IMiDs, lenalidomide and pomalidomide, in combination with zoledronic acid. Leukemia 31, 258–262 (2017). https://doi.org/10.1038/leu.2016.273

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