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1. Methods Mol Biol. 2019;1884:247-258. doi: 10.1007/978-1-4939-8885-3_17.

Molecular Characterization of Circulating Tumor Cells to Study Cancer


Immunoevasion.

Nicolazzo C(1), Gradilone A(1), Carpino G(2), Gazzaniga P(1), Raimondi C(3)(4).

Author information:
(1)Dipartimento di Medicina Molecolare, Sapienza Università di Roma, Rome, Italy.
(2)Dipartimento di Anatomia, Istologia, Medicina Forense e Scienze Ortopediche,
Sapienza Università di Roma, Rome, Italy.
(3)Dipartimento di Medicina Molecolare, Sapienza Università di Roma, Rome, Italy.
cristina.raimondi@libero.it.
(4)Dipartimento di Scienze Radiologiche, Oncologiche ed Anatomopatologiche,
Sapienza Università di Roma, Rome, Italy. cristina.raimondi@libero.it.

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.

DOI: 10.1007/978-1-4939-8885-3_17
PMID: 30465208

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