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Molecular Characterization of Circulating Tumor Cells to Study Cancer Immunoevasion
Chiara Nicolazzo1, Angela Gradilone1, Guido Carpino2
1Dipartimento di Medicina Molecolare, Sapienza Università di Roma, Rome, Italy.
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.
Insights
Circulating tumor cells (CTCs) evade immune attack by upregulating PD-L1 and undergoing epithelial-mesenchymal transition (EMT). These mechanisms help cancer cells survive in the bloodstream, highlighting new therapeutic targets for immunoevasion.
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- Circulating tumor cells (CTCs) face immune surveillance upon leaving the primary tumor.
- Immunoevasion mechanisms are crucial for CTC survival in circulation.
- The PD-1/PD-L1 axis and epithelial-mesenchymal transition (EMT) are implicated in cancer immune evasion.
Purpose of the Study:
- To detail methods for identifying PD-L1 expression in CTCs.
- To describe approaches for detecting EMT-like features in CTCs.
- To explore the interplay between EMT and immunoevasion in circulating tumor cells.
Main Methods:
- EpCAM-dependent and -independent strategies for CTC analysis.
- Assessment of PD-L1 expression on CTCs.
- Identification of EMT-associated markers in CTCs.
Main Results:
- Upregulation of PD-L1 in CTCs may facilitate survival in circulation.
- EMT plays a role in reprogramming the immune response.
- A link between EMT and immunoevasion in CTCs is emerging.
Conclusions:
- Understanding PD-L1 expression and EMT in CTCs is vital for cancer immunotherapy.
- EpCAM-dependent and -independent methods offer insights into CTC immunoevasion.
- Further research into EMT and PD-L1 in CTCs could reveal novel therapeutic targets.
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