Nuclear localization of PD-L1: artifact or reality?

  • Hara Polioudaki
  • Amanda Chantziou
  • Konstantina Kalyvianaki
  • Panagiotis Malamos
  • George Notas
  • Dimitris Mavroudis
  • Marilena Kampa
  • Elias Castanas
  • Panayiotis A. TheodoropoulosEmail author



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.


Breast 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.

Author’s contributions

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.

Compliance with ethical standards

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.


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Copyright information

© International Society for Cellular Oncology 2019

Authors and Affiliations

  • Hara Polioudaki
    • 1
  • Amanda Chantziou
    • 1
  • Konstantina Kalyvianaki
    • 2
  • Panagiotis Malamos
    • 2
  • George Notas
    • 2
  • Dimitris Mavroudis
    • 3
    • 4
  • Marilena Kampa
    • 2
  • Elias Castanas
    • 2
  • Panayiotis A. Theodoropoulos
    • 1
    Email author
  1. 1.Department of Biochemistry, School of MedicineUniversity of CreteHeraklionGreece
  2. 2.Laboratory of Experimental Endocrinology, School of MedicineUniversity of CreteHeraklionGreece
  3. 3.Department of Medical OncologyUniversity General Hospital of HeraklionHeraklionGreece
  4. 4.Laboratory of Translational Oncology, School of MedicineUniversity of CreteHeraklionGreece

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