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Cancer Immunology, Immunotherapy

, Volume 63, Issue 12, pp 1273–1284 | Cite as

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

  • Marie-Cristine Kuehnle
  • Sebastian Attig
  • Cedrik M. Britten
  • Henning Schulze-Bergkamen
  • Florian Lordick
  • Goetz von Wichert
  • Peter Thuss-Patience
  • Alexander Stein
  • Martin Schuler
  • Florian Bassermann
  • Ugur Sahin
  • Özlem Türeci
Original Article
  • 317 Downloads

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.

Keywords

Gastric adenocarcinoma Immune phenotyping Anti-tumor immune response Immunomonitoring 

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

Notes

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.

Supplementary material

262_2014_1596_MOESM1_ESM.pdf (1.1 mb)
Supplementary material 1 (PDF 1174 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Marie-Cristine Kuehnle
    • 1
  • Sebastian Attig
    • 2
    • 3
  • Cedrik M. Britten
    • 2
    • 4
  • Henning Schulze-Bergkamen
    • 5
  • Florian Lordick
    • 6
  • Goetz von Wichert
    • 7
  • Peter Thuss-Patience
    • 8
  • Alexander Stein
    • 9
    • 10
  • Martin Schuler
    • 11
    • 12
  • Florian Bassermann
    • 13
  • Ugur Sahin
    • 2
    • 4
  • Özlem Türeci
    • 1
  1. 1.Ganymed Pharmaceuticals AGMainzGermany
  2. 2.Translational Oncology (TRON), University Medical CenterJohannes Gutenberg University MainzMainzGermany
  3. 3.Experimental and Translational Oncology, University Medical CenterJohannes Gutenberg University MainzMainzGermany
  4. 4.Biontech RNA Pharmaceuticals GmbHMainzGermany
  5. 5.National Center for Tumor Diseases (NCT)Heidelberg University HospitalHeidelbergGermany
  6. 6.University Cancer Center Leipzig (UCCL)University Clinic LeipzigLeipzigGermany
  7. 7.Department of Internal MedicineSchön Klinik Hamburg EilbekHamburgGermany
  8. 8.Department of Haematology, Oncology and Tumorimmunology, Campus Virchow-KlinikumCharité - University Medicine BerlinBerlinGermany
  9. 9.Hubertus Wald Tumour CenterUniversity Cancer Center HamburgHamburgGermany
  10. 10.Department of Oncology, Hematology, BMT with Section PneumologyUniversity Medical Center Hamburg-EppendorfHamburgGermany
  11. 11.Department of Medical Oncology, West German Cancer CenterUniversity Duisburg-EssenEssenGermany
  12. 12.German Cancer Consortium (DKTK)HeidelbergGermany
  13. 13.Department of Medicine III, Klinikum rechts der IsarTechnische Universität MünchenMunichGermany

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