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DOI: 10.1055/s-2006-924673
Georg Thieme Verlag KG Stuttgart · New York
Interaktionen zwischen Tumorantigen-reaktiven T-Zellen des Knochenmarks und Tumorzellen bei Patientinnen mit Mammakarzinom
Interaction between Tumorantigen-reactive T-cells of Bone Marrow and Tumor Cells in Patients with Breast CancerPublication History
Eingang Manuskript: 8.6.2006
Eingang revidiertes Manuskript: 25.9.2006
Akzeptiert: 28.9.2006
Publication Date:
04 December 2006 (online)
![](https://www.thieme-connect.de/media/gebfra/200611/lookinside/thumbnails/10.1055-s-2006-924673-1.jpg)
Zusammenfassung
Das Mammakarzinom ist ein immunogener Tumor, der eine hohe Zahl an Tumor-assoziierten Antigenen exprimiert. Da die Tumorzellen bereits frühzeitig lymphogen und hämatogen metastasieren, kommt es schnell zu einer Konfrontation mit dem zellulären Immunsystem. Die Mammakarzinomzellen können vom zellulären Immunsystem über antigenpräsentierende Zellen erkannt werden. Nur im Knochenmark von Patientinnen im primären und metastasierten Stadium der Erkrankung konnten wir tumorantigen-reaktive CD45RO+ T-Gedächtniszellen (TMC) mittels Interferon-γ-ELISPOT-Analyse nachweisen. Die inaktiven Immunzellen können ex vivo über eine Stimulation mit TAA (Tumor-assoziierte Antigene)-gepulsten dendritischen Zellen (DC) zu Interferon-γ sezernierenden Effektorzellen aktiviert werden. Diese antigenspezifischen, reaktivierten T-Zellen (CD4+ und CD8+) entwickelten dann sowohl ex vivo als auch in vivo antitumoröse Effekte wie die Produktion von INF-γ und Perforin. Bei mit Tumorzellen beladenen immundefizienten NOD/SCID-Mäusen konnten Remissionen in 80 % beobachtet werden. Diese hoffnungsvollen Ergebnisse könnten bei passiven und aktiven Vakzinierungsstrategien eine bedeutende Rolle spielen.
Abstract
Breast cancer is an immunogenic tumor which expresses a wide range of tumor-associated antigens (TAA). As breast cancer cells are able to metastasize even in the early stages to lymph nodes and via blood to visceral organs and bone, there seems to be an immunological confrontation which takes place in the beginning of the disease. Breast cancer cells can be recognized by parts of the cellular immune system via antigen-presenting cells such as dendritic cells which present TAAs to naïve immune cells. Only in bone marrow of primary and metastatic breast cancer patients were we able to find tumorantigen-reactive CD45RO+ memory T-cells (MTC) by using interferon-γ-ELISPOT analysis. Furthermore we were able to reactivate those inactive T-cells ex vivo by stimulating them with TAA-pulsed dendritic cells. The reactivated CD8+ and CD4+ TAA-specific T-effector cells exhibited antitumoral effects like the production of INF-γ and perforin. In tumor-loaded NOD/SCID mice treated with those reactivated T-cells we found tumor regression in 80 %. These hopeful results may play an important role in further active and passive vaccination strategies.
Schlüsselwörter
Brustkrebs - Immunologie - T-Zellen - Immuntherapie
Key words
Breast cancer - immunology - T-cells - immunotherapy
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F. Schütz
Universitätsfrauenklinik Heidelberg
Vossstraße 9
69115 Heidelberg
Email: florian.schuetz@med.uni-heidelberg.de