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04.03.2021 | Pathologie

Tumormikromilieu im klassischen Hodgkin-Lymphom

verfasst von: Dr. Anja Mottok, MD/PhD

Erschienen in: Wiener klinisches Magazin | Ausgabe 3/2021

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Zusammenfassung

Das klassische Hodgkin-Lymphom (cHL) ist auf histologischer Ebene gekennzeichnet durch ein quantitativ dominierendes Begleitinfiltrat, das in Abhängigkeit vom histologischen Subtyp und EBV(Epstein-Barr-Virus)-Status eine unterschiedliche Zusammensetzung aufweist. Derzeitig gültige pathogenetische Konzepte postulieren, dass die malignen Zellen in Form der sogenannten Hodgkin- bzw. Reed-Sternberg(HRS)-Zellen eine dominante Rolle in der Rekrutierung verschiedener Immunzellen einnehmen, die wiederum zum Überleben der Tumorzellpopulation beitragen. Unterstützt wird diese Hypothese durch genetische Analysen, die entscheidend dazu beigetragen haben, relevante Mechanismen zu identifizieren, mithilfe derer sich die HRS-Zellen einer wirksamen Immunantwort entziehen können. Neben einer reduzierten bzw. defekten Antigenpräsentation bedingt durch strukturelle Chromosomenaberrationen und Mutationen in Komponenten bzw. Regulatoren der Haupthistokompatibilitätskomponenten Klasse I und II, kommen vor allem Kopienzahlzugewinne des 9p24.1-Lokus eine bedeutsame Rolle zu. Letztere resultieren zumeist in einer verstärkten Expression von Liganden des programmierten Zelltod-Proteins PD‑1, die durch die Interaktion mit diesem auf T‑Lymphozyten exprimierten Rezeptor zu einer Suppression der Immunantwort führen. Die Reversibilität dieser inhibitorischen Rezeptor-Liganden-Wechselwirkung wird klinisch in Form sog. Checkpoint-Inhibitoren genutzt, die bei Patienten mit cHL, insbesondere auch in der Rezidivsituation, mit im Vergleich zu vielen anderen Tumorentitäten imposanten Ansprechraten überzeugt haben. Ultimatives Ziel ist die Integration dieser Informationen in prognostische bzw. prädiktive Modelle, die eine rationale Risikostratifizierung und basierend darauf eine Selektion optimaler Therapieregime ermöglicht.
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Metadaten
Titel
Tumormikromilieu im klassischen Hodgkin-Lymphom
verfasst von
Dr. Anja Mottok, MD/PhD
Publikationsdatum
04.03.2021
Verlag
Springer Vienna
Erschienen in
Wiener klinisches Magazin / Ausgabe 3/2021
Print ISSN: 1869-1757
Elektronische ISSN: 1613-7817
DOI
https://doi.org/10.1007/s00740-021-00389-x