Frontiers in Oncology (Sep 2024)
Defining intra-tumoral and systemic immune biomarkers for locally advanced head-and-neck cancer – detailed protocol of a prospective, observatory multicenter trial (ImmunBioKHT) and first results of the immunophenotyping of the patients’ peripheral blood
- Anna-Jasmina Donaubauer,
- Anna-Jasmina Donaubauer,
- Anna-Jasmina Donaubauer,
- Anna-Jasmina Donaubauer,
- Benjamin Frey,
- Benjamin Frey,
- Benjamin Frey,
- Benjamin Frey,
- Manuel Weber,
- Manuel Weber,
- Manuel Weber,
- Moritz Allner,
- Moritz Allner,
- Christoph Vogl,
- Christoph Vogl,
- Omar Almajali,
- Omar Almajali,
- Lukas Kuczera,
- Lukas Kuczera,
- Henriette Tamse,
- Henriette Tamse,
- Matthias Balk,
- Matthias Balk,
- Matthias Balk,
- Sarina Müller,
- Sarina Müller,
- Sarina Müller,
- Markus Eckstein,
- Markus Eckstein,
- Markus Eckstein,
- Lilli Zülch,
- Lilli Zülch,
- Lilli Zülch,
- Lia Mogge,
- Lia Mogge,
- Lia Mogge,
- Thomas Weissmann,
- Thomas Weissmann,
- Rainer Fietkau,
- Rainer Fietkau,
- Rainer Fietkau,
- Marco Kesting,
- Marco Kesting,
- Marco Kesting,
- Heinrich Iro,
- Heinrich Iro,
- Heinrich Iro,
- Udo S. Gaipl,
- Udo S. Gaipl,
- Udo S. Gaipl,
- Udo S. Gaipl,
- Markus Hecht,
- Antoniu-Oreste Gostian,
- Antoniu-Oreste Gostian,
- Antoniu-Oreste Gostian,
- Antoniu-Oreste Gostian
Affiliations
- Anna-Jasmina Donaubauer
- Translational Radiobiology, Department of Radiation Oncology, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Anna-Jasmina Donaubauer
- Department of Radiation Oncology, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Anna-Jasmina Donaubauer
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- Anna-Jasmina Donaubauer
- Bavarian Cancer Research Center (BZKF), Erlangen, Germany
- Benjamin Frey
- Translational Radiobiology, Department of Radiation Oncology, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Benjamin Frey
- Department of Radiation Oncology, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Benjamin Frey
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- Benjamin Frey
- Bavarian Cancer Research Center (BZKF), Erlangen, Germany
- Manuel Weber
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- Manuel Weber
- Bavarian Cancer Research Center (BZKF), Erlangen, Germany
- Manuel Weber
- Department of Oral and Cranio-Maxillofacial Surgery, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Moritz Allner
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- Moritz Allner
- Department of Otolaryngology - Head & Neck Surgery, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Christoph Vogl
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- Christoph Vogl
- Department of Oral and Cranio-Maxillofacial Surgery, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Omar Almajali
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- Omar Almajali
- Department of Otolaryngology - Head & Neck Surgery, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Lukas Kuczera
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- Lukas Kuczera
- Department of Otolaryngology - Head & Neck Surgery, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Henriette Tamse
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- Henriette Tamse
- Department of Otolaryngology - Head & Neck Surgery, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Matthias Balk
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- Matthias Balk
- Bavarian Cancer Research Center (BZKF), Erlangen, Germany
- Matthias Balk
- Department of Otolaryngology - Head & Neck Surgery, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Sarina Müller
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- Sarina Müller
- Bavarian Cancer Research Center (BZKF), Erlangen, Germany
- Sarina Müller
- Department of Otolaryngology - Head & Neck Surgery, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Markus Eckstein
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- Markus Eckstein
- Bavarian Cancer Research Center (BZKF), Erlangen, Germany
- Markus Eckstein
- Institute of Pathology, Uniklinikum Erlangen, Erlangen, Germany
- Lilli Zülch
- Translational Radiobiology, Department of Radiation Oncology, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Lilli Zülch
- Department of Radiation Oncology, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Lilli Zülch
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- Lia Mogge
- Translational Radiobiology, Department of Radiation Oncology, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Lia Mogge
- Department of Radiation Oncology, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Lia Mogge
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- Thomas Weissmann
- Department of Radiation Oncology, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Thomas Weissmann
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- Rainer Fietkau
- Department of Radiation Oncology, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Rainer Fietkau
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- Rainer Fietkau
- Bavarian Cancer Research Center (BZKF), Erlangen, Germany
- Marco Kesting
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- Marco Kesting
- Bavarian Cancer Research Center (BZKF), Erlangen, Germany
- Marco Kesting
- Department of Oral and Cranio-Maxillofacial Surgery, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Heinrich Iro
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- Heinrich Iro
- Bavarian Cancer Research Center (BZKF), Erlangen, Germany
- Heinrich Iro
- Department of Otolaryngology - Head & Neck Surgery, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Udo S. Gaipl
- Translational Radiobiology, Department of Radiation Oncology, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Udo S. Gaipl
- Department of Radiation Oncology, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Udo S. Gaipl
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- Udo S. Gaipl
- Bavarian Cancer Research Center (BZKF), Erlangen, Germany
- Markus Hecht
- Department of Radiotherapy and Radiation Oncology, Saarland University Medical Center, Homburg, Saar, Germany
- Antoniu-Oreste Gostian
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- Antoniu-Oreste Gostian
- Bavarian Cancer Research Center (BZKF), Erlangen, Germany
- Antoniu-Oreste Gostian
- Department of Otolaryngology - Head & Neck Surgery, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Antoniu-Oreste Gostian
- Department of Otorhinolaryngology, Merciful Brothers Hospital St. Elisabeth, Straubing, Germany
- DOI
- https://doi.org/10.3389/fonc.2024.1451035
- Journal volume & issue
-
Vol. 14
Abstract
The approval and effectiveness of immune checkpoint inhibitors in head-and-neck squamous cell carcinoma (HNSCC) highlights the role of the immune system in this tumor entity. HNSCCs not only interacts with the immune system in the tumor tissue, but also induce systemic effects that may be additionally influenced by further factors such as the microbiome. Nonetheless, reliable immunological biomarkers that predict treatment response and outcome in HNSCC patients are lacking. The currently available biomarkers are mainly limited to analyses from tumor biopsies, while biomarkers from liquid biopsies, such as peripheral blood are not well-established. Thus, the here presented trial aims to identify interactions of intra-tumoral and systemic immune responses and to define prognostic immune signatures. Consequently, not only samples from the tumor tissue, but also from peripheral blood and the microbiome will be studied/are being evaluated and correlated with the clinical outcome. In this prospective, multi-center trial, 1000 HNSCC patients and 100 patients in the control cohort with non-tumor head-and-neck surgery will be enrolled. The local immune status from of the tumor and the microbiome will be sampled before treatment. In addition, the systemic immune status from peripheral blood will be analyzed before and after surgery and after the adjuvant and definitive radio-chemotherapy (RCT). Clinical baseline characteristics and outcome will additionally be collected. Data mining and modelling approaches will finally be applied to identify interactions of local and systemic immune parameters and to define prognostic immune signatures based on the evaluated immune markers. Approval from the institutional review board of the Friedrich-Alexander-Universität Erlangen-Nürnberg was granted in December 2021 (application number 21-440-B). By now, 150 patients have been enrolled in the intervention cohort. The results will be disseminated to the scientific audience and the general public via presentations at conferences and publication in peer-reviewed journals.
Keywords