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Impaired lymphocyte function in patients with hepatic malignancies after selective internal radiotherapy

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Abstract

The purpose of our study was to assess the immune function of patients with inoperable hepatic malignancies after treatment with selective internal radiotherapy (SIRT) and to identify possible correlations with clinical parameters. In 25 patients receiving SIRT lymphocyte proliferation and the production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10) after stimulation with mitogens and microbial antigens were tested prior to therapy, directly after therapy (day 1) and at day 2, 7 and 28 post therapy using the lymphocyte transformation test and enzyme-linked immunospot assays. Absolute counts and percentages of leukocyte and lymphocyte subsets were determined by flow cytometry. The most prominent finding was an immediate and significant (p < 0.05) decrease of lymphocyte proliferation and interferon-γ production directly after therapy which lasted until day 28 and was stronger upon stimulation with microbial antigens than with mitogens. Moreover, lymphopenia was revealed, affecting all lymphocyte subsets (CD3+, CD4+, CD8+ T cells, CD4+ CD8+ T cells, B cells and NK cells). SIRT led to a reduction in the percentage of activated HLA-DR+ monocytes and of CD45R0+ memory T cells. Higher radiation activity, the presence of liver cirrhosis, chronic kidney disease, diabetes mellitus and metastases were unfavorable factors for immunocompetence, while a better Eastern Cooperative Oncology Group performance status was associated with stronger immunological reactions. In conclusion, SIRT leads to severe impairment of cellular in vitro immune responses. Further studies are needed to assess a potential clinical impact.

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Abbreviations

CAN:

Candida albicans

Cpm:

Counts per minute

DOTATOC:

DOTA(0)-Phe(1)-Tyr(3)-octreotide

ECOG:

Eastern Cooperative Oncology Group

HCC:

Hepatocellular carcinoma

HSV-1:

Herpes simplex virus type 1

LTT:

Lymphocyte transformation test

OKT3:

Anti-CD3 monoclonal antibody

PPD:

Purified protein derivate

PWM:

Pokeweed mitogen

SIRT:

Selective internal radiotherapy

TET:

Tetanus toxoid

90Y:

Yttrium-90

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Acknowledgements

This article is a partial fulfillment of requirements for the doctor’s degree at the Medical Faculty, University of Duisburg-Essen, for Mrs. A. Domouchtsidou. We thank M. Huben, B. Nyadu and M. Praast for their excellent technical assistance.

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Authors and Affiliations

  1. Institute for Transfusion Medicine, University Hospital Essen, Virchowstraße 179, 45147, Essen, Germany

    Aglaia Domouchtsidou, Peter A. Horn & Monika Lindemann

  2. Institute of Nuclear Medicine, Helios Kliniken, Schwerin, Germany

    Vahé Barsegian

  3. Department of Nuclear Medicine, University Hospital Essen, Essen, Germany

    Stefan P. Mueller & Andreas Bockisch

  4. Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany

    Jan Best, Judith Ertle & Sotiria Bedreli

Authors
  1. Aglaia Domouchtsidou
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  2. Vahé Barsegian
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  3. Stefan P. Mueller
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  4. Jan Best
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  5. Judith Ertle
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  7. Peter A. Horn
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  8. Andreas Bockisch
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  9. Monika Lindemann
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Contributions

AD, VB, SPM, AB and ML contributed to the conception and design of the study. AD, PAH and ML wrote the report. AD, JB, JE and SB recruited the patients and took blood samples. AD performed the cellular in vitro assays. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Monika Lindemann.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval and ethical standards

The study was institutional review board approved by the ethics committee of the Medical Faculty, University Hospital Essen (approval number 09-3991), and carried out in accordance with the 1964 Helsinki Declaration.

Informed consent

All patients provided written informed consent prior to their inclusion in the study.

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Domouchtsidou, A., Barsegian, V., Mueller, S.P. et al. Impaired lymphocyte function in patients with hepatic malignancies after selective internal radiotherapy. Cancer Immunol Immunother 67, 843–853 (2018). https://doi.org/10.1007/s00262-018-2141-0

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  • DOI: https://doi.org/10.1007/s00262-018-2141-0

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