SLAMF6 deficiency augments tumor killing and skews toward an effector phenotype revealing it as a novel T cell checkpoint.
T cells
cancer
checkpoint
human
human biology
immunology
immunotherapy
inflammation
medicine
mouse
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
03 03 2020
03 03 2020
Historique:
received:
07
10
2019
accepted:
11
02
2020
pubmed:
4
3
2020
medline:
27
4
2021
entrez:
4
3
2020
Statut:
epublish
Résumé
SLAMF6 is a homotypic receptor of the Ig-superfamily whose exact role in immune modulation has remained elusive. Its constitutive expression on resting and activated T cells precludes it from being a The immune system helps to protect our bodies from illnesses and infections. Immunotherapies are medicines designed to treat diseases, such as cancer, by boosting the immune system against the condition. This is a powerful approach but so far immunotherapies have only had partial success and there is a need for further improvements. One protein called SLAMF6 is found on cells from the immune system that attack and kill cancer cells. Immunotherapies that suppress SLAMF6 on immune cells called killer T cells could increase immune system activity helping to treat cancers, particularly melanoma skin cancers. So far the potential for SLAMF6 as a target for immunotherapy has not been fully explored. Hajaj et al. created mice with killer T cells that recognized skin cancer cells and lacked SLAMF6. These modified cells were better at fighting cancer, producing more anti-cancer chemicals called cytokines and killing more cancer cells. The modified cells had a lasting effect on tumors and helped the mice to live longer. The effects could be further boosted by treating the mice in combination with other immunotherapies. SLAMF6 is a possible new target for skin cancer immunotherapy that could help more people to live longer following cancer diagnosis. The next step is to create a drug to target SLAMF6 in humans and to test it in clinical trials.
Autres résumés
Type: plain-language-summary
(eng)
The immune system helps to protect our bodies from illnesses and infections. Immunotherapies are medicines designed to treat diseases, such as cancer, by boosting the immune system against the condition. This is a powerful approach but so far immunotherapies have only had partial success and there is a need for further improvements. One protein called SLAMF6 is found on cells from the immune system that attack and kill cancer cells. Immunotherapies that suppress SLAMF6 on immune cells called killer T cells could increase immune system activity helping to treat cancers, particularly melanoma skin cancers. So far the potential for SLAMF6 as a target for immunotherapy has not been fully explored. Hajaj et al. created mice with killer T cells that recognized skin cancer cells and lacked SLAMF6. These modified cells were better at fighting cancer, producing more anti-cancer chemicals called cytokines and killing more cancer cells. The modified cells had a lasting effect on tumors and helped the mice to live longer. The effects could be further boosted by treating the mice in combination with other immunotherapies. SLAMF6 is a possible new target for skin cancer immunotherapy that could help more people to live longer following cancer diagnosis. The next step is to create a drug to target SLAMF6 in humans and to test it in clinical trials.
Identifiants
pubmed: 32122464
doi: 10.7554/eLife.52539
pii: 52539
pmc: PMC7075692
doi:
pii:
Substances chimiques
Signaling Lymphocytic Activation Molecule Family
0
Slamf6 protein, mouse
0
Banques de données
dbGaP
['phs000815.v2.p1']
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
Subventions
Organisme : International Development Research Centre
ID : 108403
Organisme : CIHR
ID : FDN-143338
Pays : Canada
Organisme : NCI NIH HHS
ID : R01 CA208756
Pays : United States
Informations de copyright
© 2020, Hajaj et al.
Déclaration de conflit d'intérêts
EH, GE, SK, SF, SM, IB, TE, SH, AV, NH, NA, RA, JC, TP, AV, ML No competing interests declared
Références
Science. 2018 Jun 15;360(6394):
pubmed: 29903938
Nat Protoc. 2014 Jan;9(1):171-81
pubmed: 24385147
Curr Opin Immunol. 2016 Feb;38:45-51
pubmed: 26682762
Annu Rev Immunol. 2011;29:665-705
pubmed: 21219180
Nat Immunol. 2019 Mar;20(3):326-336
pubmed: 30778252
J Immunol. 2018 Jan 15;200(2):408-414
pubmed: 29311382
Immunity. 2007 Aug;27(2):281-95
pubmed: 17723218
Nature. 2001 Jan 4;409(6816):97-101
pubmed: 11343121
Adv Immunol. 2008;97:177-250
pubmed: 18501771
Cold Spring Harb Perspect Biol. 2010 Mar;2(3):a002469
pubmed: 20300214
Proc Natl Acad Sci U S A. 2018 Jan 16;115(3):E468-E477
pubmed: 29282323
Nat Immunol. 2019 Apr;20(4):447-457
pubmed: 30833791
J Immunol. 1989 Aug 1;143(3):798-801
pubmed: 2568380
J Immunol. 1990 Mar 1;144(5):1646-53
pubmed: 2155264
J Immunol. 2017 Mar 1;198(5):2182-2190
pubmed: 28100680
Cancer Immunol Res. 2018 Feb;6(2):127-138
pubmed: 29305520
Immunity. 2012 Jun 29;36(6):1003-16
pubmed: 22683123
Nat Immunol. 2016 Apr;17(4):387-96
pubmed: 26878112
J Biol Chem. 2008 Jul 11;283(28):19255-64
pubmed: 18482989
J Exp Med. 2001 Aug 6;194(3):235-46
pubmed: 11489943
Br J Cancer. 2002 May 20;86(10):1534-9
pubmed: 12085200
Semin Immunopathol. 2010 Jun;32(2):157-71
pubmed: 20146065
Front Cell Dev Biol. 2019 Jul 03;7:110
pubmed: 31334230
Cancer Immunol Res. 2019 Sep;7(9):1485-1496
pubmed: 31315913
Immunity. 2012 Jun 29;36(6):986-1002
pubmed: 22683125
PLoS One. 2014 May 14;9(5):e96650
pubmed: 24827921
Nat Protoc. 2007;2(9):2049-56
pubmed: 17853860
J Immunol. 2014 May 1;192(9):4202-9
pubmed: 24688028
J Immunol. 2013 Mar 1;190(5):2121-8
pubmed: 23355739
Cell. 2000 Mar 17;100(6):655-69
pubmed: 10761931