Implementing liquid biopsies into clinical decision making for cancer immunotherapy

Dagmar Quandt, Hans Dieter Zucht, Arno Amann, Anne Wulf-Goldenberg, Carl Borrebaeck, Michael Cannarile, Diether Lambrechts, Herbert Oberacher, James Garrett, Tapan Nayak, Michael Kazinski, Charles Massie, Heidi Schwarzenbach, Michele Maio, Robert Prins, Björn Wendik, Richard Hockett, Daniel Enderle, Mikkel Noerholm, Hans Hendriks, Heinz Zwierzina and Barbara Seliger _

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Oncotarget. 2017; 8:48507-48520. https://doi.org/10.18632/oncotarget.17397

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Dagmar Quandt1, Hans Dieter Zucht2, Arno Amann3, Anne Wulf-Goldenberg4, Carl Borrebaeck5, Michael Cannarile6, Diether Lambrechts7, Herbert Oberacher8, James Garrett9, Tapan Nayak10, Michael Kazinski11, Charles Massie12, Heidi Schwarzenbach13, Michele Maio14, Robert Prins15, Björn Wendik16, Richard Hockett17, Daniel Enderle18, Mikkel Noerholm18, Hans Hendriks19, Heinz Zwierzina3 and Barbara Seliger1

1Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, Halle, Germany

2Protagen, Dortmund, Germany

3Department of Haematology and Oncology, Medical University Innsbruck, Innsbruck, Austria

4Experimental Pharmacology and Oncology, Berlin-Buch GmbH, Berlin, Germany

5Create Health Translational Cancer Center, Lund University, Lund, Sweden

6Roche Pharmaceutical Research and Early Development, Roche Innovation Center, Munich, Germany

7Laboratory for Translational Genetics, VIB Center for Cancer Biology, Leuven, Belgium

8Institute of Legal Medicine and Core Facility Metabolomics, Medical University of Innsbruck, Innsbruck, Austria

9Global Drug Development, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA

10Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland

11Qiagen, Hilden, Germany

12CRUK Cambridge Institute, Cambridge, UK

13University Medical Center Hamburg-Eppendorf, Department of Tumor Biology Hamburg, Hamburg, Germany

14Medical Oncology and Immunotherapy, University Hospital of Siena, Siena, Italy

15Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA

16Perkin Elmer, Hamburg, Germany

17Biodesix, Boulder, Colorado, USA

18Exosome Diagnostics GmbH, Martinsried, Germany

19Hendriks Pharmaceutical Consulting, Purmerend, The Netherlands

Correspondence to:

Barbara Seliger, email: [email protected]

Keywords: liquid biopsy, biomarker, tumor, high throughput analysis, immunotherapy

Received: February 08, 2017     Accepted: April 04, 2017     Published: April 24, 2017


During the last decade, novel immunotherapeutic strategies, in particular antibodies directed against immune checkpoint inhibitors, have revolutionized the treatment of different malignancies leading to an improved survival of patients. Identification of immune-related biomarkers for diagnosis, prognosis, monitoring of immune responses and selection of patients for specific cancer immunotherapies is urgently required and therefore areas of intensive research. Easily accessible samples in particular liquid biopsies (body fluids), such as blood, saliva or urine, are preferred for serial tumor biopsies.

Although monitoring of immune and tumor responses prior, during and post immunotherapy has led to significant advances of patients’ outcome, valid and stable prognostic biomarkers are still missing. This might be due to the limited capacity of the technologies employed, reproducibility of results as well as assay stability and validation of results. Therefore solid approaches to assess immune regulation and modulation as well as to follow up the nature of the tumor in liquid biopsies are urgently required to discover valuable and relevant biomarkers including sample preparation, timing of the collection and the type of liquid samples. This article summarizes our knowledge of the well-known liquid material in a new context as liquid biopsy and focuses on collection and assay requirements for the analysis and the technical developments that allow the implementation of different high-throughput assays to detect alterations at the genetic and immunologic level, which could be used for monitoring treatment efficiency, acquired therapy resistance mechanisms and the prognostic value of the liquid biopsies.

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