Nuclear localization of PD-L1: artifact or reality?

Background The levels of expression and membrane localization of programmed cell death ligand 1 (PD-L1), an immune checkpoint type I transmembrane glycoprotein, are related to the clinical response of anti-PD-L1/PD-1 therapy. Although the biologically relevant localization of PD-L1 is on the plasma...

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Bibliographic Details
Published in:Cellular oncology (Dordrecht) 2019-04, Vol.42 (2), p.237-242
Main Authors: Polioudaki, Hara, Chantziou, Amanda, Kalyvianaki, Konstantina, Malamos, Panagiotis, Notas, George, Mavroudis, Dimitris, Kampa, Marilena, Castanas, Elias, Theodoropoulos, Panayiotis A.
Format: Article
Language:English
Subjects:
Apoptosis
Biomedical and Life Sciences
Biomedicine
Breast cancer
Cancer Research
Cell death
Commentary
Cytoplasm
Immune checkpoint
Localization
Membrane proteins
Oncology
Pathology
PD-1 protein
PD-L1 protein
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Summary:Background The levels of expression and membrane localization of programmed cell death ligand 1 (PD-L1), an immune checkpoint type I transmembrane glycoprotein, are related to the clinical response of anti-PD-L1/PD-1 therapy. Although the biologically relevant localization of PD-L1 is on the plasma membrane of cancer cells, it has also been reported to be in the cytoplasm and sometimes in the nucleus. Furthermore, it has been claimed that chemotherapeutics can modify PD-L1 expression and/or its nuclear localization. Results Data from our group suggest that the nuclear localization of PD-L1, and other plasma membrane proteins as well, could be an artifact resulting from inadequate experimental conditions during immunocytochemical studies. Mild detergent and rigorous fixation conditions should be used in order to preserve the membrane localization and to prevent an erroneous translocation of PD-L1 and other non-interconnected membrane proteins, such as CD24, into other cellular compartments including the nucleus, of untreated and chemotherapeutically treated breast cancer cells. Conclusion We propose that well-specified and rigorously followed protocols should be applied to immunocytochemical diagnostic techniques, especially to those related to individualized diagnosis and treatment.
ISSN:2211-3428
2211-3436
DOI:10.1007/s13402-018-00419-7