Natural killer cell lines kill autologous β2-microglobulin-deficient melanoma cells: Implications for cancer immunotherapy
- †Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, and ¶Surgery Branch, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and §Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 01238
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Contributed by Jack L. Strominger
Abstract
Cancer vaccines used to generate specific cytotoxic T lymphocytes are not effective against tumor cells that have lost or suppressed expression of their class I major histocompatibility complex proteins. This loss is common in some cancers and particularly in metastatic lesions. We show that β2-microglobulin-deficient class I-negative melanoma variants derived from patients undergoing specific T cell therapy are lysed by heterologous as well as autologous natural killer (NK) lines and clones, but not by specific T cells. Moreover, the minor NK cell fraction but not the major T cell fraction derived from heterologous lymphokine activated killer cells kills those tumor cell lines. ICAM-1 expression by the different class I protein deficient tumors was correlated with their sensitivity to lysis by NK cells. Adoptive autologous NK therapy may be an important supplement to consider in the design of new cancer immunotherapies.
Footnotes
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↵ ‡ A.P. and O.M. contributed equally to this paper.
- ABBREVIATIONS:
- CTL,
- cytotoxic T lymphocyte;
- MHC,
- major histocompatibility complex;
- β2m,
- β2-microglobulin;
- NK,
- natural killer;
- NKIR,
- NK inhibitory receptors;
- LAK,
- lymphokine-activated killer;
- HLA,
- human leukocyte antigen;
- PBMC,
- peripheral blood mononuclear cell;
- E/T,
- effector-to-target cell ratio;
- IL-2,
- interleukin 2;
- ATCC,
- American Type Culture Collection
- Copyright © 1997, The National Academy of Sciences of the USA
