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Impairment of lymphocyte function following yttrium-90 DOTATOC therapy

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Abstract

The radiolabeled somatostatin analogue, yttrium-90 DOTA-d-Phe(1)-Tyr(3)-octreotide (DOTATOC), is currently applied to treat advanced somatostatin receptor-positive tumors, e.g., neuroendocrine tumors of the pancreas, lung or gut. However, effects of this treatment on antimicrobial immune responses are not yet defined. In 20 patients treated with DOTATOC, cellular in vitro immune function was determined. Their antimicrobial lymphocyte responses were assessed by lymphocyte transformation test and enzyme-linked immunospot—measuring lymphocyte proliferation and on a single cell level production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10)—prior to therapy, at day 1, day 7 and day 90 post-therapy. Proliferative lymphocyte responses and interferon-γ production after in vitro stimulation with microbial antigens were non-significantly suppressed at day 1 and significantly (p < 0.05) at day 7 versus pre-therapy. In vitro immune responses did not fully recover until day 90. In contrast, at day 1 interleukin-10 production was significantly (p < 0.05) increased. Taken together, we observed a decrease in pro-inflammatory immune responses after DOTATOC therapy. Patients with versus without bone metastases displayed significantly (p < 0.05) lower cellular immune responses toward several microbial antigens. Progressive disease and higher tumor burden could also be defined as factors associated with impaired immune function. Spearman correlation analysis indicated that cellular in vitro immunity was positively correlated with kidney function; better kidney function led to stronger immune responses. In conclusion, DOTATOC therapy caused a decrease in in vitro immune responses against microorganisms. The clinical impact needs to be evaluated in further studies.

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Abbreviations

Cpm:

Counts per minute

DOTATOC:

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

DTPA:

Diethylene-triamine-pentaacetate

ELISpot:

Enzyme-linked immunospot

68Ga:

Gallium-68

IFN:

Interferon

IL:

Interleukin

LTT:

Lymphocyte transformation test

OKT3:

Anti-CD3 monoclonal antibody

PBMCs:

Peripheral blood mononuclear cells

PET/CT:

Positron emission tomography together with computed tomography

90Sr:

Strontium-90

90Y:

Yttrium-90

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Acknowledgments

This article is a partial fulfillment of requirements for the doctor’s degree at the Medical Faculty, University of Essen, Germany, for Mr. C. Hueben.

Ethical standards

All patients provided written informed consent prior to their inclusion in the study. The study was approved by the institutional review board and carried out in accordance with the Helsinki Declaration of 1964, as revised in 2000.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

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

    Vahé Barsegian

  2. Institute for Transfusion Medicine, University Hospital, Essen, Germany

    Christian Hueben, Peter A. Horn & Monika Lindemann

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

    Stefan P. Mueller, Thorsten D. Poeppel & Andreas Bockisch

Authors
  1. Vahé Barsegian
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  2. Christian Hueben
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  3. Stefan P. Mueller
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  4. Thorsten D. Poeppel
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  5. Peter A. Horn
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  6. Andreas Bockisch
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  7. Monika Lindemann
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Correspondence to Monika Lindemann.

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Barsegian, V., Hueben, C., Mueller, S.P. et al. Impairment of lymphocyte function following yttrium-90 DOTATOC therapy. Cancer Immunol Immunother 64, 755–764 (2015). https://doi.org/10.1007/s00262-015-1687-3

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  • DOI: https://doi.org/10.1007/s00262-015-1687-3

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