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Ly49G2 receptor blockade reduces tumor burden in a leukemia model but not in a solid tumor model

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Background

NK cell activity is regulated in part by inhibitory receptors that bind to MHC class I molecules. It is possible to enhance NK cell cytotoxicity against tumor cells by preventing the interaction of these inhibitory receptors with their MHC class I ligands.

Results

In this study, we determined that Ly49G2 is an inhibitory receptor in AKR mice for self-MHC class I, and AKR Ly49G2 has an identical sequence to BALB/c Ly49G2. Blockade of Ly49G2 receptors in vivo resulted in decreased growth of BW-Sp3 lymphoma cells when the tumor cells were given i.v. but not when the tumor cells were inoculated into the flank forming a solid tumor. However, NK cells were involved in inhibiting the growth of BW-Sp3 tumor cells in the flank.

Conclusion

These data demonstrate that the effectiveness of inhibitory receptor blockade depends upon the tissue location of the tumor cells.

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Acknowledgments

This work was supported by a grant from the National Institutes of Health, USA and the National Cancer Institute (CA101748, AI07363). We thank Martin Grundy for technical assistance with the generation of Ly49G2 antibody fragments, Gary Ward and Alice Givan (Englert Cell Analysis Laboratory, Norris Cotton Cancer Center) for cell sorting, and the Animal Resource Center staff for assistance with animal care.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Dartmouth Medical School, 6W Borwell Bldg, One Medical Center Dr, Lebanon, NH, 03756, USA

    Melissa A. Barber, Tong Zhang, Bethany A. Gagne & Charles L. Sentman

  2. Lab of Cellular and Molecular Immunology, Department of Molecular and Cellular Interactions, VIB, Brussels, Belgium

    Jo A. Van Ginderachter & Patrick De Baetselier

  3. Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium

    Jo A. Van Ginderachter & Patrick De Baetselier

Authors
  1. Melissa A. Barber
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  2. Tong Zhang
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  6. Charles L. Sentman
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Correspondence to Charles L. Sentman.

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Barber, M.A., Zhang, T., Gagne, B.A. et al. Ly49G2 receptor blockade reduces tumor burden in a leukemia model but not in a solid tumor model. Cancer Immunol Immunother 57, 655–662 (2008). https://doi.org/10.1007/s00262-007-0404-2

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  • DOI: https://doi.org/10.1007/s00262-007-0404-2

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