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Treatment-induced changes of lymphocyte subsets in patients with adenoid cystic carcinoma of the head and neck

  • Head & Neck
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Purpose

Adenoid cystic carcinoma (ACC) of the head and neck is a rare and highly malignant tumor, characterized by perineural growth and early distant metastases. The composition of immune cells in the peripheral blood and the tumor microenvironment is critical to tumor growth and control. However, little is known about the frequency and function of the relevant immune cell subsets in this entity.

Methods

In ACC patients (n = 11) and matched healthy donors (n = 11), the frequency of peripheral blood T and B cells was measured by flow cytometry at different treatment stages of disease (24 samples). Cells were further characterized by their expression of CCR7, PD-1, CD39 and CD73. Tumor-infiltrating lymphocytes (TIL) were analyzed by immunohistochemistry for ten patients and for three patients by flow cytometry.

Results

CD4+ T cells had significantly lower frequency after radiotherapy (RT). All other cell frequencies, including Treg, were stable through course of the disease. In B cells, CD73 was reduced after RT. CCR7 expression on T and B cells in patients with relapse/metastases (R/M) differed significantly from patients with active disease. PD-1 remained stable. Treg were more present in TIL compared to peripheral blood.

Conclusion

Composition of lymphocyte subgroups behaves similar to squamous cell carcinoma in the head and neck, except for Treg, which remained stable. Nevertheless, the CD4+/Treg ratio was lower after RT, which could stand for an immunosuppressive effect in these patients. Therefore, it could be beneficial treating ACC with combined RT and immunomodulatory drugs.

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Abbreviations

ACC:

Adenoid cystic carcinoma

TIL:

Tumor-infiltrating lymphocytes

RT:

Radiotherapy

R/M:

Relapse/metastases

CAP:

Cisplatin, doxorubicin, and cyclophosphamide

ADO:

Adenosine

PBMC:

Peripheral blood mononuclear cells

NC:

Normal controls

AD:

Active disease

mAbs:

Monoclonal antibodies

FSC:

Forward scatter

SSC:

Side scatter

MFI:

Mean fluorescence intensity

SRG:

Surgery

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Acknowledgements

We thank Katja Hasch, Gabriela Cudek and Monika Jerg for their support in performing the experiments.

Funding

This study was funded by German Research Foundation (DFG) Grant # SCHU 2536/3 and the International Graduate School in Molecular Medicine Ulm.

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Authors and Affiliations

  1. Department of Otorhinolaryngology, Head and Neck Surgery, Ulm University Medical Center, University of Ulm, Frauensteige 12, 89075, Ulm, Germany

    S. S. Jeske, C. Brunner, M. N. Theodoraki, T. K. Hoffmann, P. J. Schuler & Johannes Doescher

  2. Institute of Pathology, University of Ulm, Ulm, Germany

    S. E. Weissinger

  3. Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty Mannheim, University Hospital Mannheim, University Heidelberg, Heidelberg, Germany

    J. A. Veit

  4. Department of Endocrinology, Diabetology, Angiology and Internal Medicine, Neuperlach Medical Center, Neuperlach, Germany

    U. Huber

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  1. S. S. Jeske
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  2. S. E. Weissinger
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  3. J. A. Veit
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  4. C. Brunner
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  6. M. N. Theodoraki
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  8. P. J. Schuler
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Contributions

SSJ, UH and SEW performed experiments; SSJ and SEW prepared figures; JV and JD provided patient samples; SSJ, PJS and JD designed research and wrote the paper; MNT, CB, and TKH edited the paper.

Corresponding author

Correspondence to Johannes Doescher.

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Conflict of interest

There are no potential conflicts of interest to disclose. The research was supported by the German Research Foundation (DFG) Grant # SCHU 2536/3 (PJS) and by the International Graduate School in Molecular Medicine Ulm (SSJ).

Ethical approval

This article does not contain any studies with animals performed by any of the authors. All procedures performed in studies involving human participants were in accordance with the ethical standards approved by the local ethical committee (#255/14).

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Informed consent was obtained from all individual participants included in the study.

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Jeske, S.S., Weissinger, S.E., Veit, J.A. et al. Treatment-induced changes of lymphocyte subsets in patients with adenoid cystic carcinoma of the head and neck. Eur Arch Otorhinolaryngol 276, 1465–1473 (2019). https://doi.org/10.1007/s00405-019-05363-2

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  • DOI: https://doi.org/10.1007/s00405-019-05363-2

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