IL15 Stimulation with TIGIT Blockade Reverses CD155-mediated NK-Cell Dysfunction in Melanoma.
Animals
Antigens, Differentiation, T-Lymphocyte
/ genetics
CD8-Positive T-Lymphocytes
/ drug effects
Cell Line, Tumor
Cell Proliferation
/ drug effects
Humans
Interleukin-15
/ genetics
Killer Cells, Natural
/ drug effects
Melanoma
/ blood
Mice
Receptors, Immunologic
/ antagonists & inhibitors
Receptors, Virus
/ genetics
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
15 10 2020
15 10 2020
Historique:
received:
13
02
2020
revised:
03
05
2020
accepted:
22
06
2020
pubmed:
28
6
2020
medline:
24
11
2021
entrez:
28
6
2020
Statut:
ppublish
Résumé
Natural killer (NK) cells play a critical role in tumor immunosurveillance. Multiple activating and inhibitory receptors (IR) regulate NK-cell-mediated tumor control. The IR T-cell immunoglobulin and ITIM domain (TIGIT) and its counter-receptor CD226 exert opposite effects on NK-cell-mediated tumor reactivity. We evaluated the frequency, phenotype, and functions of NK cells freshly isolated from healthy donors and patients with melanoma with multiparameter flow cytometry. We assessed TIGIT and CD226 cell surface expression and internalization upon binding to CD155. We evaluated the role of IL15 and TIGIT blockade in increasing NK-cell-mediated cytotoxicity NK cells are present at low frequencies in metastatic melanoma, are dysfunctional, and downregulate both TIGIT and CD226 expression. As compared with TIGIT Our findings support the development of novel combinatorial immunotherapy with IL15 and TIGIT blockade to promote NK-cell-mediated destruction of MHC class I-deficient melanoma, which are refractory to CD8
Identifiants
pubmed: 32591463
pii: 1078-0432.CCR-20-0575
doi: 10.1158/1078-0432.CCR-20-0575
pmc: PMC8045409
mid: NIHMS1607778
doi:
Substances chimiques
Antigens, Differentiation, T-Lymphocyte
0
CD226 antigen
0
Interleukin-15
0
Receptors, Immunologic
0
Receptors, Virus
0
TIGIT protein, human
0
poliovirus receptor
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5520-5533Subventions
Organisme : NCI NIH HHS
ID : P50 CA121973
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA222203
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA228181
Pays : United States
Organisme : NIH HHS
ID : S10 OD019942
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
©2020 American Association for Cancer Research.
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