Memory-like Differentiation Enhances NK Cell Responses to Melanoma.
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:
01 09 2021
01 09 2021
Historique:
received:
08
03
2021
revised:
01
05
2021
accepted:
14
06
2021
pubmed:
1
7
2021
medline:
5
4
2022
entrez:
30
6
2021
Statut:
ppublish
Résumé
Treatment of advanced melanoma is a clinical challenge. Natural killer (NK) cells are a promising cellular therapy for T cell-refractory cancers, but are frequently deficient or dysfunctional in patients with melanoma. Thus, new strategies are needed to enhance NK-cell antitumor responses. Cytokine-induced memory-like (ML) differentiation overcomes many barriers in the NK-cell therapeutics field, resulting in potent cytotoxicity and enhanced cytokine production against blood cancer targets. However, the preclinical activity of ML NK against solid tumors remains largely undefined. Phenotypic and functional alterations of blood and advanced melanoma infiltrating NK cells were evaluated using mass cytometry. ML NK cells from healthy donors (HD) and patients with advanced melanoma were evaluated for their ability to produce IFNγ and kill melanoma targets NK cells in advanced melanoma exhibited a decreased cytotoxic potential compared with blood NK cells. ML NK cells differentiated from HD and patients with advanced melanoma displayed enhanced IFNγ production and cytotoxicity against melanoma targets. This included ML differentiation enhancing melanoma patients' NK-cell responses against autologous targets. The ML NK-cell response against melanoma was partially dependent on the NKG2D- and NKp46-activating receptors. Furthermore, in xenograft NSG mouse models, human ML NK cells demonstrated superior control of melanoma, compared with conventional NK cells. Blood NK cells from allogeneic HD or patients with advanced melanoma can be differentiated into ML NK cells for use as a novel immunotherapeutic treatment for advanced melanoma, which warrants testing in early-phase clinical trials.
Identifiants
pubmed: 34187852
pii: 1078-0432.CCR-21-0851
doi: 10.1158/1078-0432.CCR-21-0851
pmc: PMC8416927
mid: NIHMS1717890
doi:
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
4859-4869Subventions
Organisme : NCI NIH HHS
ID : T32 CA009621
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA171963
Pays : United States
Organisme : NCI NIH HHS
ID : K12 CA167540
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA205239
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA224083
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA091842
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA248277
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007088
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA204115
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK052574
Pays : United States
Informations de copyright
©2021 The Authors; Published by the American Association for Cancer Research.
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