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Semin Immunol. 2017 Jun;31:20-29. doi: 10.1016/j.smim.2017.08.002. Epub 2017 Sep 6.

Natural killer cell-mediated immunosurveillance of human cancer.

Author information

1
Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway; The KG Jebsen Centre for Cancer Immunotherapy, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
2
Center for Hematology and Regenerative Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
3
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Center for Hematology and Regenerative Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
4
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
5
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Cell Therapy Institute, Nova Southeastern University, Ft Lauderdale, FL, USA. Electronic address: hans-gustaf.ljunggren@ki.se.

Abstract

The contribution of natural killer (NK) cells to immunosurveillance of human cancer remains debatable. Here, we discuss advances in several areas of human NK cell research, many of which support the ability of NK cells to prevent cancer development and avoid relapse following adoptive immunotherapy. We describe the molecular basis for NK cell recognition of human tumor cells and provide evidence for NK cell-mediated killing of human primary tumor cells ex vivo. Subsequently, we highlight studies demonstrating the ability of NK cells to migrate to, and reside in, the human tumor microenvironment where selection of tumor escape variants from NK cells can occur. Indirect evidence for NK cell immunosurveillance against human malignancies is provided by the reduced incidence of cancer in individuals with high levels of NK cell cytotoxicity, and the significant clinical responses observed following infusion of human NK cells into cancer patients. Finally, we describe studies showing enhanced tumor progression, or increased cancer incidence, in patients with inherited and acquired defects in cellular cytotoxicity. All these observations have in common that they, either indirectly or directly, suggest a role for NK cells in mediating immunosurveillance against human cancer. This opens up for exciting possibilities with respect to further exploring NK cells in settings of adoptive immunotherapy in human cancer.

KEYWORDS:

Cancer; HLA; Immune escape; Immunoediting; Immunosurveillance; Immunotherapy; Induced self; Leukemia; MHC class I; Missing self; NK cell; Natural killer cell; Tumor

PMID:
28888619
DOI:
10.1016/j.smim.2017.08.002
[Indexed for MEDLINE]

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