Cellular liaisons of natural killer lymphocytes in immunology and immunotherapy of cancer

Abstract

There is compelling evidence for the role of natural killer (NK) cells in tumor immunosurveillance and their beneficial effects on many experimentally successful immunotherapy strategies. NK cells mediate cell contact-dependent cellular cytotoxicity and produce pro-inflammatory cytokines, but do not rearrange antigen receptors. Their activation depends on various germline-encoded receptors, including CD16, which mediates recognition of antibody-coated target cells. NK cytotoxicity is checked by a repertoire of inhibitory receptors that scan adequate expression of major histocompatibility complex class I molecules on the potential target cell. Functional cross-talk of NK and dendritic cells suggests a critical role for NK cells in the initiation and regulation of cellular immunity. Considerable knowledge on the molecular basis of NK recognition/activation contrasts with a lack of successful translational research on these matters. However, there is plenty of opportunity for targeted intervention of inhibitory/activatory surface receptors and for adoptive cell therapy with autologous or allogeneic NK cells.

Keywords::

• adaptive immunity
• cancer immunology
• DC
• immunotherapy
• NK cell
• NKG2D

Acknowledgements

Financial support was from Ministerio de Educación y Ciencia (MEC-SAF2005-03131), Departamento de Educación del Gobierno de Navarra, Redes Temáticas de Investigación Cooperativa RETIC, FIS PI060932 and ‘UTE for project FIMA’. OM and AA are recipients of scholarships from Ministerio de Educación (MEC) and Fondo de Investigación Sanitaria (BEFI).

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