Nuclear localization of PD-L1: artifact or reality?
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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.
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.
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.
KeywordsBreast cancer PD-L1 Doxorubicin Nuclear localization Plasma membrane
Programmed cell death ligand 1
This work was partly supported by grant KA4969 from the Special Account for Research Funds of the University of Crete.
HP, AC, KK, PM: acquisition and analysis of data, revising the manuscript. GN, DM, MK: analysis and interpretation of data, revising the manuscript. EC: analysis and interpretation of data, contribution to study planning, drafting and revising the manuscript. PAT: conception and design of the study, analysis and interpretation of the data, drafting and revising the manuscript. All authors read and approved the final manuscript.
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The authors declare that they have no competing interests.
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