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Induction of tumor-specific T cell memory by NK cell–mediated tumor rejection

Nature Immunology volume 3, pages 83–90 (2002)Cite this article

Abstract

Natural killer (NK) cells may modulate the development of adaptive immune responses, but until now there has been little evidence to support this hypothesis. We investigated the primary and secondary immunity elicited by various tumor cell lines that express CD70 and interact with CD70 ligand (CD27), which is constitutively expressed on NK cells. CD70 expression enhanced primary tumor rejection in vivo as well as T cell immunity against secondary tumor challenge. Primary rejection of major histocompatibility complex (MHC) class I–deficient RMA-S.CD70 tumor cells was mediated by NK cells and perforin- and interferon-γ–dependent mechanisms. This NK cell–mediated process also efficiently evoked the subsequent development of tumor-specific cytotoxic and T helper type 1 responses to the parental, MHC class I–sufficient, RMA tumor cells. Thus CD27-CD70 interactions provide a key link between innate NK cell responses and adaptive T cell immunity.

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Figure 1: Expression of CD70 on tumor cells.
Figure 2: Tumor rejection promoted by CD70 expression.
Figure 3: CD70 stimulates NK cell–mediated protection that requires perforin and IFN-γ.
Figure 4: Tumor CD70 expression evokes tumor-specific T cell memory.
Figure 5: NK cell–mediated primary rejection evokes tumor-specific T cell immunity.
Figure 6: Specific CTL responses evoked by CD70-driven NK cell–mediated tumor rejection.
Figure 7: Specific TH1 responses evoked by CD70-driven NK cell–mediated tumor rejection.
Figure 8: Priming of secondary T cell immunity requires NK cells and IFN-γ.

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Acknowledgements

We thank C. Hall and the staff of the PMCI for their maintenance and care of the mice in this project. Supported by Human Frontier Science Program and National Health and Medical Research Council of Australia (M. J. S.) and Diabetes Australia (D. I. G.).

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Authors and Affiliations

  1. Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Institute, St. Andrews Place, East Melbourne, Victoria, Australia

    Janice M. Kelly, Phillip K. Darcy & Mark J. Smyth

  2. Department of Pathology and Immunology, Monash Medical School, Commercial Road, Prahran, Victoria, Australia

    Jessica L. Markby & Dale I. Godfrey

  3. Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan

    Kazuyoshi Takeda & Hideo Yagita

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Correspondence to Mark J. Smyth.

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Kelly, J., Darcy, P., Markby, J. et al. Induction of tumor-specific T cell memory by NK cell–mediated tumor rejection. Nat Immunol 3, 83–90 (2002). https://doi.org/10.1038/ni746

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