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Radioimmuntherapie

Radioimmunotherapy

Zusammenfassung

Hintergrund

Die Strahlentherapie wird eingesetzt, um eine lokale Tumorkontrolle im bestrahlten Areal zu erreichen. Im letzten Jahrzehnt stiegen die Erkenntnisse, dass die Strahlentherapie neben der Abtötung von Tumorzellen auch immunmodulatorische Eigenschaften besitzt.

Ziel

Wesentliche Grundlagen der immunmodulatorischen Effekte der Strahlentherapie werden erläutert und insbesondere der klinische Nutzen bei Kombination von Strahlentherapie mit Immuncheckpointinhibitoren dargestellt.

Ergebnisse

Eine Strahlentherapie kann durch Auslösen des immunogenen Zelltods von Tumorzellen und Veränderungen des Tumormikromilieus tumorspezifische Immunantworten triggern. Allerdings wurde eine klinische Relevanz solcher systemisch immunologischer Effekte einer lokalen Bestrahlung in der Vergangenheit nur sehr selten beobachtet, was vermutlich daran liegt, dass eine Bestrahlung auch immunsupprimierend wirken kann. Durch die Kombination von lokaler Strahlentherapie mit Immuncheckpointinhibitoren können antitumorale Immunantworten verstärkt und immunsupprimierenden Effekten entgegengewirkt werden. Solche Therapiestrategien werden aktuell in zahlreichen klinischen Studien untersucht. Durch sie wurden beim nichtkleinzelligen Lungenkarzinom (Stadium III) mit dem PD-L1-Inhibitor Durvalumab nach definitiver Radiochemotherapie beachtliche Ergebnisse erzielt.

Schlussfolgerung

Die Kombination von Strahlentherapie mit Immuncheckpointinhibitoren ist ein effektives Therapiekonzept, das aktuell in zahlreichen Studien untersucht wird und beim nichtkleinzelligen Lungenkarzinom bereits in der klinischen Routine eingesetzt wird.

Abstract

Background

Radiotherapy is used to achieve local tumor control in the irradiated area. In the last decade, there has been increasing evidence that radiotherapy has immunomodulatory properties in addition to killing tumor cells.

Purpose

Essential principles of the immunomodulatory effects of radiotherapy are explained and, in particular, the clinical benefits of radiotherapy in combination with immune checkpoint inhibitors are presented.

Results

Radiotherapy can trigger tumor-specific immune responses by inducing immunogenic cell death of tumor cells and alterations of the tumor microenvironment. However, clinical relevance of such systemic immunologic effects of local irradiation has been observed only very rarely in the past, which is probably due to the fact that irradiation can also induce immunosuppressive effects. By combining local radiotherapy with immune checkpoint inhibitors, antitumor immune responses can be enhanced and immunosuppressive effects can be counteracted. Such therapeutic strategies are currently being investigated in numerous clinical trials and have achieved remarkable results in non-small cell lung cancer (stage III) with the PD-L1 inhibitor durvalumab after definitive radiochemotherapy.

Conclusion

The combination of radiotherapy with immune checkpoint inhibitors is an efficient concept that is currently being investigated in numerous studies and has already entered clinical routine in non-small cell lung cancer.

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Correspondence to M. Hecht.

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Interessenkonflikt

M. Hecht: Merck Serono (Beratungsfunktion, Referententätigkeit, Honorare, Reisekosten, Forschungsförderung); MSD (Beratungsfunktion, Referententätigkeit, Honorare, Reisekosten, Forschungsförderung); AstraZeneca (Forschungsförderung); Novartis (Forschungsförderung); BMS (Beratungsfunktion, Honorare, Referententätigkeit); Teva (Reisekosten). U.S. Gaipl und R. Fietkau geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Hecht, M., Gaipl, U.S. & Fietkau, R. Radioimmuntherapie. Onkologe (2021). https://doi.org/10.1007/s00761-021-01011-9

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Schlüsselwörter

  • Immuncheckpointinhibitoren
  • PD‑1
  • Immunogener Zelltod
  • Immuntherapie
  • Strahlentherapie

Keywords

  • Immune checkpoint inhibitors
  • PD‑1
  • Immunogenic cell death
  • Immunotherapy
  • Radiotherapy