Natürliche Killerzellen und Leukämiekontrolle

Zusammenfassung

Natürliche Killer-(NK-)Zellen sind spezialisierte Lymphozyten, die v. a. für die Bekämpfung von Virusinfektionen und Tumorentstehung als „first line of defence“ wichtig sind. Die klinische Relevanz der NK-Zelle im Rahmen der Tumorbekämpfung konnte dabei insbesondere im Bereich der allogenen hämatopoietischen Stammzelltransplantation (HSZT) nachgewiesen werden. So führen Inkompatibilitäten in den HLA-Klasse-I-kodierten Liganden der NK-Zellrezeptoren zwischen Spender und Empfänger zu einer Erkennung myeloischer Leukämien durch NK-Zellen, was sich in einem gesteigerten Graft-versus-Leukemia-(GvL-)Effekt klinisch manifestiert. Die molekulare Basis für diese Beobachtungen sind inhibitorische NK-Zellrezeptoren der KIR-Familie, die nach dem Prinzip der „Missing-Self “-Erkennung durch das Fehlen spezifischer HLA-A-, -B- oder -C-kodierter Liganden zur NK-Zellaktivierung führen. In den letzten Jahren wurden verschiedene genetische Risikokonstellationen der hochpolymorphen KIR und HLA-Klasse-I-Liganden beschrieben, die zu einer verbesserten Auswahl von Fremdspendern führen könnten. In dieser Arbeit wird eine Übersicht über die aktuellen Befunde auf diesem Gebiet gegeben und die Relevanz des KIR-HLA-Klasse-I-Systems für die Entwicklung einer NK-zellbasierten Immuntherapie diskutiert.

Abstract

Natural Killer (NK) cells are specialized lymphocytes that serve important roles in combating viral infections and tumor development as a first line of defense. The clinical relevance of NK cells in the field of tumor surveillance could be clearly shown in the setting of allogeneic stem cell transplantation. Incompatibilities in the HLA class I-encoded ligands of NK cell receptors between donor and recipient lead to recognition of leukemia by alloreactive NK cells, which clinically translates into increased graft-versus-leukemia (GvL) effects. The molecular basis of these observations are inhibitory NK cell receptors of the KIR family, which lead to NK cell activation via „missing self“ recognition triggered by the absence of cognate HLA-A, -B, or -C encoded ligands. In recent years, genetic risk constellations could be defined for the highly polymorphic KIR genes as well as for combinations of KIR genes and their HLA class I ligands, which have the potential to improve stem cell donor selection. In this review, an overview is given about recent developments in this field and the potential of exploiting the KIR/HLA class I ligand system for developing novel NK cell-based immunotherapies.

Schlüsselwörter

NK-Zellen - Leukämie - Onkologie - KIR - ALL - AML - Stammzelltransplantation

Key words

NK cells - leukemia - cancer - KIR - ALL - AML - HSCT

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