HLA-G gene editing in tumor cell lines as a novel alternative in cancer immunotherapy.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
12 11 2021
12 11 2021
Historique:
received:
22
01
2021
accepted:
22
10
2021
entrez:
13
11
2021
pubmed:
14
11
2021
medline:
27
1
2022
Statut:
epublish
Résumé
Cancer immunotherapies based mainly on the blockade of immune-checkpoint (IC) molecules by anti-IC antibodies offer new alternatives for treatment in oncological diseases. However, a considerable proportion of patients remain unresponsive to them. Hence, the development of novel clinical immunotherapeutic approaches and/or targets are crucial.W In this context, targeting the immune-checkpoint HLA-G/ILT2/ILT4 has caused great interest since it is abnormally expressed in several malignancies generating a tolerogenic microenvironment. Here, we used CRISPR/Cas9 gene editing to block the HLA-G expression in two tumor cell lines expressing HLA-G, including a renal cell carcinoma (RCC7) and a choriocarcinoma (JEG-3). Different sgRNA/Cas9 plasmids targeting HLA-G exon 1 and 2 were transfected in both cell lines. Downregulation of HLA-G was reached to different degrees, including complete silencing. Most importantly, HLA-G - cells triggered a higher in vitro response of immune cells with respect to HLA-G + wild type cells. Altogether, we demonstrated for the first time the HLA-G downregulation through gene editing. We propose this approach as a first step to develop novel clinical immunotherapeutic approaches in cancer.
Identifiants
pubmed: 34773056
doi: 10.1038/s41598-021-01572-0
pii: 10.1038/s41598-021-01572-0
pmc: PMC8589947
doi:
Substances chimiques
HLA-G Antigens
0
RNA, Guide
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
22158Subventions
Organisme : Consejo Nacional de Investigaciones Científicas y Técnicas
ID : PIP 112-20150100723
Organisme : Scientific and Technical Research Fund (FONCyT)
ID : PICT-2015-1469
Informations de copyright
© 2021. The Author(s).
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