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Phenotyping of peripheral blood mononuclear cells of patients with advanced heavily pre-treated adenocarcinoma of the stomach and gastro-esophageal junction

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Abstract

Immunotherapeutic approaches are emerging as promising new treatment options for patients with solid cancers. The host immune system in cancer patients is dysfunctional due to a number of reasons. The level of immunosuppression is variable at the time of diagnosis and depends on the particular cancer entity, stage, and prior anti-cancer therapies. For many cancer entities, the immune alterations of the respective patient population have not been further characterized even though a patient’s immunophenotype may be prognostic for the course of the disease or predictive for clinical/biological response to immunotherapy. In this study, we used flow cytometry to determine the phenotype of peripheral blood mononuclear cells (PBMCs) from 30 patients with heavily pre-treated, advanced adenocarcinoma of the stomach and gastro-esophageal junction. The frequencies and activation status of relevant immune effector populations were determined in PBMCs and compared to those of healthy individuals. This report provides comprehensive immune phenotyping data of a patient population with a high medical need.

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Abbreviations

ADCC:

Antibody-dependent cell-mediated cytotoxicity

CDC:

Complement-dependent cytotoxicity

CIC:

Cancer Immunotherapy Consortium

CIMT:

Association for Cancer Immunotherapy

CTLA-4:

Cytotoxic T-lymphocyte antigen-4

CV:

Coefficients of variance

DC:

Dendritic cell

DMSO:

Dimethyl sulfoxide

FDA:

Food and Drug Administration

FoxP3:

Forkhead box protein 3

HD:

Healthy donors

IgG1:

Immunoglobulin G subclass I

M:

Metastasis

mAb:

Monoclonal antibody

MDSCs:

Myeloid-derived suppressor cells

N:

Node

NK cells:

Natural killer cells

n.s.:

Not significant

P:

Patient

PBMCs:

Peripheral blood mononuclear cells

PBS:

Phosphate-buffered saline

PD-1:

Programmed death-1

PDL-1:

Programmed death ligand-1

RCC:

Renal cell carcinoma

T:

Tumor

Tregs:

Regulatory T cells

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Acknowledgments

We wish to thank Helene Schroeder and Nicole Bidmon for sample processing and Daniela Kirsch and Richard Rae for their technical assistance with performing flow cytometry. We thank Marc Roller, Marlene Knippenberg, and Vilmos Posevitz for excellent scientific writing support. The majority of samples were provided by clinical trial centers represented by authors of this manuscript as part of their participation in the phase II clinical trial testing the safety and single-agent activity of the therapeutic antibody IMAB362. We wish to acknowledge also all investigators and clinical trial centers, who have provided single patient samples: Ulrike Helbig, Hospital Braunschweig, Wolff Schmiegel, University Hospital Bochum, Salah-Eddin Al-Batran, Hospital Nordwest Frankfurt, Joern Ruessel, University Hospital Halle a. d. Saale, Susanna Hegewisch-Becker, Hematologisch-Onkologische Praxis Eppendorf, Hamburg and Albrecht Hoffmeister, University Hospital Leipzig (all Germany).

Conflict of interest

M.-C. Kuehnle and Ö. Türeci are employees of Ganymed Pharmaceuticals AG; U. Sahin and Ö. Türeci are inventors of patents on claudin18.2 and hold stock of Ganymed Pharmaceuticals AG. U. Sahin is consultant of Ganymed Pharmaceuticals AG. S. Attig, C. M. Britten, H. Schulze-Bergkamen, F. Lordick, G. von Wichert, P. Thuss-Patience, A. Stein, M. Schuler, and F. Bassermann declare no conflict of interests.

Author information

Authors and Affiliations

  1. Ganymed Pharmaceuticals AG, An der Goldgrube 12, 55131, Mainz, Germany

    Marie-Cristine Kuehnle & Özlem Türeci

  2. Translational Oncology (TRON), University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany

    Sebastian Attig, Cedrik M. Britten & Ugur Sahin

  3. Experimental and Translational Oncology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany

    Sebastian Attig

  4. Biontech RNA Pharmaceuticals GmbH, Mainz, Germany

    Cedrik M. Britten & Ugur Sahin

  5. National Center for Tumor Diseases (NCT), Heidelberg University Hospital, Heidelberg, Germany

    Henning Schulze-Bergkamen

  6. University Cancer Center Leipzig (UCCL), University Clinic Leipzig, Leipzig, Germany

    Florian Lordick

  7. Department of Internal Medicine, Schön Klinik Hamburg Eilbek, Hamburg, Germany

    Goetz von Wichert

  8. Department of Haematology, Oncology and Tumorimmunology, Campus Virchow-Klinikum, Charité - University Medicine Berlin, Berlin, Germany

    Peter Thuss-Patience

  9. Hubertus Wald Tumour Center, University Cancer Center Hamburg, Hamburg, Germany

    Alexander Stein

  10. Department of Oncology, Hematology, BMT with Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Alexander Stein

  11. Department of Medical Oncology, West German Cancer Center, University Duisburg-Essen, Essen, Germany

    Martin Schuler

  12. German Cancer Consortium (DKTK), Heidelberg, Germany

    Martin Schuler

  13. Department of Medicine III, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

    Florian Bassermann

Authors
  1. Marie-Cristine Kuehnle
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  2. Sebastian Attig
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  3. Cedrik M. Britten
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  4. Henning Schulze-Bergkamen
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  5. Florian Lordick
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  6. Goetz von Wichert
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  7. Peter Thuss-Patience
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  8. Alexander Stein
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  9. Martin Schuler
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  10. Florian Bassermann
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  11. Ugur Sahin
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  12. Özlem Türeci
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Corresponding author

Correspondence to Özlem Türeci.

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Kuehnle, MC., Attig, S., Britten, C.M. et al. Phenotyping of peripheral blood mononuclear cells of patients with advanced heavily pre-treated adenocarcinoma of the stomach and gastro-esophageal junction. Cancer Immunol Immunother 63, 1273–1284 (2014). https://doi.org/10.1007/s00262-014-1596-x

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  • DOI: https://doi.org/10.1007/s00262-014-1596-x

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