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NK cell-mediated targeting of human cancer and possibilities for new means of immunotherapy

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Abstract

Insights into the molecular basis for natural killer (NK) cell recognition of human cancer have been obtained in recent years. Here, we review current knowledge on the molecular specificity and function of human NK cells. Evidence for NK cell targeting of human tumors is provided and new strategies for NK cell-based immunotherapy against human cancer are discussed. Based on current knowledge, we foresee a development where more cancers may be subject to treatment with drugs or other immunomodulatory agents affecting NK cells, either directly or indirectly. We also envisage a possibility that certain forms of cancers may be subject to treatment with adoptively transferred NK cells, either alone or in combination with other therapeutic interventions.

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Abbreviations

AICD:

Activation induced cell death

ADCC:

Antibody mediated cellular cytotoxicity

AML:

Acute myeloid leukemia

ATG:

Anti-thymocyte globulin

ATM:

Ataxia telangiectasia, mutated

ATR:

ATM- and Rad3-related

CR:

Complete remission

DC:

Dendritic cell

DLI:

Donor lymphocyte infusion

EBV:

Epstein-Barr virus

Fas L:

Fas ligand

Flt-3 L:

Flt-3 ligand

GMP:

Good manufacturing practice

GVH:

Graft-versus-host

GVT:

Graft-versus-tumor

GVHD:

Graft-versus-host-disease

HLA:

Human leukocyte antigen

IFN:

Interferon

KIR:

Killer-Ig-like receptors

LAK:

Lymphokine activated killer

MHC:

Major histocompatibility complex

NCR:

Natural cytotoxicity receptor

NK:

Natural killer

SCF:

Stem cell factor

SCT:

Stem cell transplantation

TNF:

Tumor necrosis factor

Treg:

Regulatory T

TRAIL:

TNF-related apoptosis-inducing ligand

UL:

Unique long

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Acknowledgments

We are supported by the Swedish Foundation for Strategic Research, the Swedish Research Council, the Swedish Cancer Society, the Royal Swedish Academy of Sciences, the Swedish Children’s Cancer Society, the Cancer Society of Stockholm, the Karolinska Institutet, and the Karolinska University Hospital.

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Authors and Affiliations

  1. Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86, Stockholm, Sweden

    Karl-Johan Malmberg, Yenan T. Bryceson, Mattias Carlsten, Sandra Andersson, Andreas Björklund, Niklas K. Björkström, Bettina C. Baumann, Cyril Fauriat & Hans-Gustaf Ljunggren

  2. Division of Hematology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86, Stockholm, Sweden

    Evren Alici & M. Sirac Dilber

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  1. Karl-Johan Malmberg
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  2. Yenan T. Bryceson
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  11. Hans-Gustaf Ljunggren
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Correspondence to Hans-Gustaf Ljunggren.

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This article is a symposium paper from the conference “The European Society for Medical Oncology (ESMO) and the European Society for Cancer Immunology and Immunotherapy (ESCII) International Symposium on Immunology”, held in Athens, Greece, on 15–17 November 2007.

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Malmberg, KJ., Bryceson, Y.T., Carlsten, M. et al. NK cell-mediated targeting of human cancer and possibilities for new means of immunotherapy. Cancer Immunol Immunother 57, 1541–1552 (2008). https://doi.org/10.1007/s00262-008-0492-7

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