Nuclear localization of PD-L1: artifact or reality?
Breast cancer
Doxorubicin
Nuclear localization
PD-L1
Plasma membrane
Journal
Cellular oncology (Dordrecht)
ISSN: 2211-3436
Titre abrégé: Cell Oncol (Dordr)
Pays: Netherlands
ID NLM: 101552938
Informations de publication
Date de publication:
Apr 2019
Apr 2019
Historique:
accepted:
20
12
2018
pubmed:
27
1
2019
medline:
30
7
2019
entrez:
26
1
2019
Statut:
ppublish
Résumé
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.
Sections du résumé
BACKGROUND
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 30680705
doi: 10.1007/s13402-018-00419-7
pii: 10.1007/s13402-018-00419-7
doi:
Substances chimiques
B7-H1 Antigen
0
Glycoproteins
0
Membrane Proteins
0
Doxorubicin
80168379AG
Types de publication
Journal Article
Langues
eng
Pagination
237-242Subventions
Organisme : Special Account for Research Funds of the University of Crete
ID : KA4969
Références
Nat Med. 2002 Aug;8(8):793-800
pubmed: 12091876
Cancer Res. 2004 Nov 15;64(22):8334-40
pubmed: 15548702
J Cell Biochem. 2006 Aug 15;98(6):1570-83
pubmed: 16552725
Nat Med. 2007 Jan;13(1):84-8
pubmed: 17159987
J Recept Signal Transduct Res. 2008;28(1-2):15-28
pubmed: 18437627
Oncogene. 2009 Jan 15;28(2):306-12
pubmed: 18850006
J Cell Sci. 2009 Apr 15;122(Pt 8):1111-8
pubmed: 19299461
Cell Prolif. 2009 Aug;42(4):434-47
pubmed: 19486015
Cancer Lett. 2010 Feb 1;288(1):99-106
pubmed: 19619935
Breast Cancer Res. 2010;12(4):R48
pubmed: 20626886
Eur J Pharm Biopharm. 2010 Nov;76(3):514-24
pubmed: 20638475
Nat Methods. 2010 Nov;7(11):865-6
pubmed: 20881966
Oncogene. 2014 Feb 6;33(6):756-70
pubmed: 23376851
J Biol Chem. 2013 Sep 6;288(36):25838-50
pubmed: 23884413
Int J Clin Exp Pathol. 2014 Aug 15;7(9):6015-23
pubmed: 25337246
PLoS One. 2015 Aug 18;10(8):e0135528
pubmed: 26284927
Virchows Arch. 2016 May;468(5):511-25
pubmed: 26915032
Handb Exp Pharmacol. 2017;235:311-329
pubmed: 27316910
Sci Rep. 2016 Jul 01;6:28910
pubmed: 27363678
Dev Cell. 2016 Aug 8;38(3):227-33
pubmed: 27505414
Small GTPases. 2017 Jan 26;:1-10
pubmed: 28125336
Cell Rep. 2017 May 9;19(6):1189-1201
pubmed: 28494868
Int J Cancer. 2017 Oct 1;141(7):1402-1412
pubmed: 28614911
Cancer Discov. 2017 Jul;7(7):675-693
pubmed: 28630051
Cancer Res. 2017 Sep 15;77(18):4858-4867
pubmed: 28674079
Appl Immunohistochem Mol Morphol. 2018 Feb;26(2):83-93
pubmed: 28719380
Nature. 2017 Sep 7;549(7670):101-105
pubmed: 28813417
Br J Cancer. 2018 Feb 6;118(3):312-324
pubmed: 29123260
Appl Immunohistochem Mol Morphol. 2019 Apr;27(4):287-294
pubmed: 29135534
Cell Oncol (Dordr). 2018 Apr;41(2):107-121
pubmed: 29470831
Oncogene. 2018 Aug;37(34):4639-4661
pubmed: 29765155
Semin Cancer Biol. 2018 Dec;53:189-200
pubmed: 30261276