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Regulatorische T-Zellen und NK-Zellen bei Krebspatienten

Regulatory T cells and NK cells in cancer patients

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Zusammenfassung

NK-Zellen stellen die effektivsten Zellen des Immunsystems zur Bekämpfung von infizierten und entarteten Zellen dar. Regulatorische T-Zellen und ihre beiden Hauptuntergruppen, die natürlich vorkommenden nTreg und die tumorassoziierten induzierten Treg (iTreg), spielen eine wichtige Rolle bei der antitumoralen Immunantwort bei Krebspatienten. In der vorliegenden Arbeit werden die interzellulären Wechselwirkungen dieser Zellgruppen bei Tumorpatienten, insbesondere mit einem Kopf-Hals-Karzinom, dargestellt. Entscheidende Wechselwirkungen zwischen diesen Zellen und den Krebszellen wurden in umfassenden experimentellen Analysen beobachtet. So ließen sich zunächst tumorassoziierte iTreg in einer speziellen humanen Kultur generieren und anschließend im autologen System verschiedene phänotypische und funktionelle Zusammenhänge zwischen diesen Zellen, nTreg, NK-Zellen und Tumorzellen überprüfen. iTreg führten zu einer Verstärkung der Aktivität von naiven NK-Zellen in der Gegenwart von Tumorzellen, wohingegen NK-Zellen, die mit Interleukin-2 aktiviert wurden, durch iTreg und nTreg deutlich in ihrer zytotoxischen Funktion gehemmt wurden. Die Arbeitsgruppe des Autors hat neue Einblicke in die komplexe Regulation der menschlichen NK-Zellen und regulatorische T-Zellen im Tumormikromilieu dokumentiert. Dies kann für ein besseres Verständnis der antitumoralen Immunantwort und für die Weiterentwicklung von immuntherapeutischen Strategien von Bedeutung sein.

Abstract

NK cells represent the cells of the immune system most effective for eradication of infected or neoplastic cells. Regulatory T cells and the two main subgroups thereof—the naturally occurring nTregs and the tumor-associated induced Tregs (iTregs)—play an important role in the antitumor immune response in cancer patients. The current study explores the intercellular interactions of these groups of cells in tumor patients, particularly in head and neck cancer. Critical interactions between these cells and the cancer cells could be observed in extensive experimental analyses. Firstly, we generated tumor-associated iTregs in a specific human culture. Subsequently, various phenotypic and functional relationships between these cells, nTregs, NK cells and tumor cells were analyzed in an autologous system. Although the activity of naive NK cells was enhanced by iTregs in the presence of tumor cells, the cytotoxic function of NK cells activated by interleukin-2 was markedly inhibited by iTregs and nTregs. Our group was able to document new insights into the complex regulation of human NK cells and regulatory T cells in the tumor microenvironment. These new insights may be of relevance for an improved understanding of the antitumor immune response and the development of immunotherapeutic strategies.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. C. Bergmann gibt an, dass kein Interessenkonflikt besteht.

Alle im vorliegenden Manuskript beschriebenen Untersuchungen am Menschen wurden mit Zustimmung der zuständigen Ethik-Kommission, im Einklang mit nationalem Recht sowie gemäß der Deklaration von Helsinki von 1975 (in der aktuellen, überarbeiteten Fassung) durchgeführt. Von allen beteiligten Patienten liegt eine Einverständniserklärung vor.

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  1. Klinik für Hals-Nasen-Ohren-Heilkunde, Universitätsklinikum Essen (AöR), Hufelandstr. 55, 45147, Essen, Deutschland

    C. Bergmann

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Correspondence to C. Bergmann.

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Anton-von-Tröltsch-Preisträger 2013.

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Bergmann, C. Regulatorische T-Zellen und NK-Zellen bei Krebspatienten. HNO 62, 406–414 (2014). https://doi.org/10.1007/s00106-014-2874-9

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  • DOI: https://doi.org/10.1007/s00106-014-2874-9

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