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Molecular Characterization of Circulating Tumor Cells to Study Cancer Immunoevasion

  • Chiara Nicolazzo
  • Angela Gradilone
  • Guido Carpino
  • Paola Gazzaniga
  • Cristina Raimondi
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1884)

Abstract

Cancer cells leaving the primary tumor immunosuppressive microenvironment become vulnerable to active immune surveillance and require mechanisms of immunoevasion to survive in the circulation. Studies have identified several pathways by which circulating tumor cells (CTCs) might escape the immune system/immunotherapy attack. The PD-1/PD-L1 axis is an immune checkpoint regulator, playing a major role in maintaining self-tolerance. It is now well recognized that tumor cells co-opt the PD-1/PD-L1 axis of immune regulation to interfere with cytotoxic T lymphocyte function. Transcriptional changes in CTCs, leading to the upregulation of PD-L1, might enable them to survive in circulation. Very recent data revealed a previously unappreciated role of epithelial-mesenchymal transition (EMT) in reprogramming the immune response in the local tumor microenvironment and a mutual regulation between EMT and immunoevasion is becoming apparent. In this chapter, we will describe in detail both EpCAM-dependent and -independent approaches that allow the identification of PD-L1 expression and EMT-like features in circulating tumor cells.

Key words

CTCs PD-L1 Immunoevasion EMT ScreenCell® CellSearch® 

References

  1. 1.
    Patel SP, Kurzrock R (2015) PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther 14:847–856CrossRefGoogle Scholar
  2. 2.
    Remon J, Chaput N, Planchard D (2016) Predictive biomarkers for programmed death-1/programmed death ligand immune checkpoint inhibitors in nonsmall cell lung cancer. Curr Opin Oncol 28:122–129CrossRefGoogle Scholar
  3. 3.
    Buder A, Tomuta C, Filipits M (2016) The potential of liquid biopsies. Curr Opin Oncol 28:130–134CrossRefGoogle Scholar
  4. 4.
    Mazel M, Jacot W, Pantel K et al (2015) Frequent expression of PD-L1 on circulating breast cancer cells. Mol Oncol 9:1773–1782CrossRefGoogle Scholar
  5. 5.
    Nicolazzo C, Raimondi C, Mancini M et al (2016) Monitoring PD-L1 positive circulating tumor cells in non-small cell lung cancer patients treated with the PD-1 inhibitor Nivolumab. Sci Rep 6:31726CrossRefGoogle Scholar
  6. 6.
    Terry S, Savagner P, Ortiz-Cuaran S et al (2017) New insights into the role of EMT in tumor immune escape. Mol Oncol 11:824–846CrossRefGoogle Scholar
  7. 7.
    Raimondi C, Carpino G, Nicolazzo C et al (2017) PD-L1 and epithelial-mesenchymal transition in circulating tumor cells from non-small cell lung cancer patients: a molecular shield to evade immune system? OncoImmunology 6(12):e1315488.  https://doi.org/10.1080/2162402X.2017.1315488CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Paoletti C, Li Y, Muñiz MC et al (2015) Significance of circulating tumor cells in metastatic triple-negative breast cancer patients within a randomized, phase II trial: TBCRC 019. Clin Cancer Res 21:2771–2779CrossRefGoogle Scholar
  9. 9.
    Carpino G, Cardinale V, Renzi A et al (2015) Activation of biliary tree stem cells within peribiliary glands in primary sclerosing cholangitis. J Hepatol 63:1220–1228CrossRefGoogle Scholar
  10. 10.
    Coumans F, Terstappen L (2015) Detection and characterization of circulating tumor cells by the cellsearch approach. Methods Mol Biol 1347:263–278CrossRefGoogle Scholar
  11. 11.
    Woititz CA (2008) Guideline for the use and optimization of user-defined markers. CellSearch®. https://www.cellsearchruo.com/sites/default/files/Guideline-for-Use-and-Optimization-of-User-Defined-Markers.pdf
  12. 12.
    Nicolazzo C, Raimondi C, Francescangeli F et al (2017) EpCAM-expressing circulating tumor cells in colorectal cancer. Int J Biol Markers 32(4):e415–e420.  https://doi.org/10.5301/ijbm.5000284CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Chiara Nicolazzo
    • 1
  • Angela Gradilone
    • 1
  • Guido Carpino
    • 2
  • Paola Gazzaniga
    • 1
  • Cristina Raimondi
    • 1
    • 3
  1. 1.Dipartimento di Medicina MolecolareSapienza Università di RomaRomeItaly
  2. 2.Dipartimento di Anatomia, Istologia, Medicina Forense e Scienze OrtopedicheSapienza Università di RomaRomeItaly
  3. 3.Dipartimento di Scienze Radiologiche, Oncologiche ed AnatomopatologicheSapienza Università di RomaRomeItaly

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