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Renal cell carcinoma-infiltrating natural killer cells express differential repertoires of activating and inhibitory receptors and are inhibited by specific HLA class I allotypes.
Int. J. Cancer 106, 905-912 (2003)
Among tumor-infiltrating lymphocytes (TILs) directly isolated from renal cell carcinomas (RCCs), we found substantial numbers of natural killer (NK) cells in most tumor tissues. They could be identified reliably in situ with an antibody directed against the activating receptor (AR) NKp46 that is exclusively expressed by all NK cells. NK-enriched TILs (NK-TILs) showed cytotoxicity against major histocompatibility complex (MHC) class I-negative cell lines. The ability to detect lysis of target cells was dependent on the percentage of NK cells within the TILs, and cytotoxicity was only observed after overnight activation with low-dose interleukin-2 (IL-2). Infiltrating NK cells were found to express various inhibitory receptors (IRs); among these the CD94/NKG2A receptor complex was overrepresented compared to the autologous peripheral blood mononuclear cell (PBMC) population. Other IRs were underrepresented, indicating that NK subpopulations vary in their tumor-infiltrating capacity. IRs expressed by NK-TILs are functional since receptor engagement with MHC class I ligands presented by human leukocyte antigen (HLA)-transfected target cell lines was able to inhibit NK-mediated cytotoxicity. NK-TILs were also able to lyse autologous or allogeneic tumor cell lines in vitro. This activity correlated with low HLA class I surface expression since lysis could be inhibited by interferon (IFN)-gamma-expressing RCC transductants that displayed a higher surface density of HLA class I molecules. Therefore, NK cells infiltrating tumor tissues have an inherent ability to recognize transformed cells, but they require cytokine activation and are sensitive to inhibition by IR ligands.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
natural killer cells; major histocompatibility complex; NK receptors; tumor-infiltrating lymphocytes; renal cell carcinoma; killer cell inhibitory receptors
ISSN (print) / ISBN
0020-7136
e-ISSN
1097-0215
Zeitschrift
International Journal of Cancer
Quellenangaben
Band: 106,
Heft: 6,
Seiten: 905-912
Verlag
Wiley
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Molecular Immunology (IMI)