Nuclear Localization of PD-L1: Artifact or Reality?

Overview

Journal Cell Oncol (Dordr)

Publisher Springer

Date 2019 Jan 26

PMID 30680705

Citations 12

Authors

Hara Polioudaki

Amanda Chantziou

Konstantina Kalyvianaki

Panagiotis Malamos

George Notas

Dimitris Mavroudis

Marilena Kampa

Elias Castanas

Panayiotis A Theodoropoulos

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Exploring the dynamics of Programmed Death-Ligand 1 in canine lymphoma: unraveling mRNA amount, surface membrane expression and plasmatic levels.

Ubiali A, Conti L, DallAra P, De Maria R, Aresu L, Moretti P Front Vet Sci. 2024; 11:1412227.

PMID: 39132435 PMC: 11310028. DOI: 10.3389/fvets.2024.1412227.

PD-L1 deglycosylation promotes its nuclear translocation and accelerates DNA double-strand-break repair in cancer.

Shu Z, Dwivedi B, Switchenko J, Yu D, Deng X Nat Commun. 2024; 15(1):6830.

PMID: 39122729 PMC: 11316045. DOI: 10.1038/s41467-024-51242-8.

The nuclear transportation of PD-L1 and the function in tumor immunity and progression.

Qu L, Jin J, Lou J, Qian C, Lin J, Xu A Cancer Immunol Immunother. 2022; 71(10):2313-2323.

PMID: 35246703 PMC: 10992355. DOI: 10.1007/s00262-022-03176-7.

Programmed death ligand 1 signals in cancer cells.

Kornepati A, Vadlamudi R, Curiel T Nat Rev Cancer. 2022; 22(3):174-189.

PMID: 35031777 PMC: 9989967. DOI: 10.1038/s41568-021-00431-4.

The Role of Oncogenes and Redox Signaling in the Regulation of PD-L1 in Cancer.

Glorieux C, Xia X, Huang P Cancers (Basel). 2021; 13(17).

PMID: 34503236 PMC: 8431622. DOI: 10.3390/cancers13174426.

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