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Natural killer cells

Targeting tumour cells

Nature Reviews Immunology volume 1, page 91 (2001)Cite this article

The formulation of the missing-self hypothesis predicted the existence of receptors on NK cells that inhibit their activity and which recognize MHC class I molecules. Many of these receptors have now been identified. Recent work has also identified several activating NK receptors, including the lectin-like molecule NKG2D, whose engagement provides dominant activating signals to the NK cell. Previous work by Tom Spies' group showed that NK cells can kill NKG2D ligand-expressing cells in vitro. The mouse ligands for NKG2D are retinoic acid early inducible-1 (Rae-1) and H60, which are expressed by some tumour cells, but not by normal adult cells.

Both groups looked for direct evidence to support the idea that tumour cells ectopically expressing ligands for NKG2D could stimulate antitumour responses by NK cells. The Raulet group used a retroviral expression system to express Rae1β and H60 in three mouse tumour cell lines that express MHC class I molecules — EL4 thymoma cells, RMA T-cell lymphoma cells (which were used in the original Kärre study) and B16-BL6 melanoma cells. Transduced EL4 and B16-BL6 cells that were injected subcutaneously into recipient mice were rapidly and completely rejected. Tumour cells were rejected in wild-type mice depleted of CD8+ T cells and in Rag−/− mice (which lack T and B cells), but grew in Rag−/− mice depleted of NK cells, indicating that conventional NK cells are responsible for the rejection. Rae1β- or H60-transduced RMA cells were also rejected in wild-type mice, but rejection required both CD8+ T cells and NK cells.

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ORIGINAL RESEARCH PAPERS

  1. Diefenbach, A., Jensen, E. R., Jamieson, A. M. & Raulet, D. H. Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity. Nature 413, 165–171 (2001) http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11557981&dopt=Abstract

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  2. Cerwenka, A., Baron, J. L. & Lanier L. L. Ectopic expression of retinoic acid early inducible-1 gene (RAE-1) permits natural killer cell-mediated rejection of a MHC class I-bearing tumor in vivo. Proc. Natl Acad. Sci. USA 98, 11521–11526 (2001) http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11562472&dopt=Abstract

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Authors
  1. Elaine Bell
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Lewis Lanier's lab

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Bell, E. Targeting tumour cells. Nat Rev Immunol 1, 91 (2001). https://doi.org/10.1038/35100537

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