Epilogue: Killer Lymphocytes as Tools for Future Immunotherapeutic Approaches

  • Walter Gottlieb Land


The Epilogue of Part VII is dedicated to the enormous potential of innate lymphoid cells and unconventional T cells to be used as an instrument for future immunotherapeutic approaches, in particular, anticancer therapy. In fact, the potential therapeutic use of these cells has already entered clinical trials. For example, clinical adoptive transfer studies with the use of natural killer cells have already demonstrated effective anti-tumor effects with a low rate of rejection and side effects. Likewise, analogues of alpha-galactosylceramide and phosphoantigen analogues, which stimulate robust responses from type I natural killer T cells and gammadelta T cells, respectively, or adoptive transfer of these cells, have already found the way into clinical trials in cancer patients. Moreover, emerging approaches targeting unconventional T cells are discussed to be well suited to accompany conventional vaccines by enhancing the adaptive immune response in an adjuvant-like manner. For example, analogues of alpha-galactosylceramide were shown to promote natural killer T cell–dendritic cell interactions, which in turn can activate natural killer cells while simultaneously boosting adaptive T cell and B cell immunity to microbial or tumor antigens. The Epilogue ends up by arguing that much effort has been recently made to improve immunotherapeutic efforts with the use of innate lymphoid cells or unconventional T cells and that the clinical applicability of these approaches has been clearly demonstrated. However, further research is still needed to optimize such therapeutic procedures; in particular, the simultaneous application of potent DAMPs has to be seriously considered in each of those modalities.


  1. 1.
    Martín-Antonio B, Suñe G, Perez-Amill L, Castella M, Urbano-Ispizua A. Natural killer cells: angels and devils for immunotherapy. Int J Mol Sci. 2017;18:1868. Available from: CrossRefGoogle Scholar
  2. 2.
    Fang F, Xiao W, Tian Z. NK cell-based immunotherapy for cancer. Semin Immunol. 2017;31:37–54. Available from: CrossRefGoogle Scholar
  3. 3.
    Pressey JG, Adams J, Harkins L, Kelly D, You Z, Lamb LS. In vivo expansion and activation of γδ T cells as immunotherapy for refractory neuroblastoma: a phase 1 study. Medicine (Baltimore). 2016;95:e4909. Available from: CrossRefGoogle Scholar
  4. 4.
    Aoki T, Matsushita H, Hoshikawa M, Hasegawa K, Kokudo N, Kakimi K. Adjuvant combination therapy with gemcitabine and autologous γδ T-cell transfer in patients with curatively resected pancreatic cancer. Cytotherapy. 2017;19:473–85. Available from: CrossRefGoogle Scholar
  5. 5.
    Exley MA, Friedlander P, Alatrakchi N, Vriend L, Yue S, Sasada T, et al. Adoptive transfer of invariant NKT cells as immunotherapy for advanced melanoma: a phase I clinical trial. Clin Cancer Res. 2017;23:3510–9. Available from: CrossRefGoogle Scholar
  6. 6.
    Waldowska M, Bojarska-Junak A, Roliński J. A brief review of clinical trials involving manipulation of invariant NKT cells as a promising approach in future cancer therapies. Cent Eur J Immunol. 2017;2:181–95. Available from: CrossRefGoogle Scholar
  7. 7.
    Gao X, Mi Y, Guo N, Xu H, Xu L, Gou X, et al. Cytokine-induced killer cells as pharmacological tools for cancer immunotherapy. Front Immunol. 2017;8:774. Available from: CrossRefGoogle Scholar
  8. 8.
    Godfrey DI, Uldrich AP, McCluskey J, Rossjohn J, Moody DB. The burgeoning family of unconventional T cells. Nat Immunol. 2015;16:1114–23. Available from: CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.University of StrasbourgMolecular ImmunoRheumatology, Laboratory of Excellence TransplantexStrasbourgFrance

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