c-Rel Is a Myeloid Checkpoint for Cancer Immunotherapy.
Journal
Nature cancer
ISSN: 2662-1347
Titre abrégé: Nat Cancer
Pays: England
ID NLM: 101761119
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
entrez:
18
1
2021
pubmed:
19
1
2021
medline:
19
1
2021
Statut:
ppublish
Résumé
Immunotherapy that targets lymphoid cell checkpoints holds great promise for curing cancer. However, a majority of cancer patients do not respond to this form of therapy. In addition to lymphoid cells, myeloid cells play essential roles in controlling immunity to cancer. Whether myeloid checkpoints exist that can be targeted to treat cancer is not well established. Here we show that c-Rel, a member of the nuclear factor (NF)-B family, specified the generation of myeloid-derived suppressor cells (MDSCs) by selectively turning on pro-tumoral genes while switching off anti-tumoral genes through a c-Rel enhanceosome. c-Rel deficiency in myeloid cells markedly inhibited cancer growth in mice, and pharmaceutical inhibition of c-Rel had the same effect. Combination therapy that blocked both c-Rel and the lymphoid checkpoint protein PD1 was more effective in treating cancer than blocking either alone. Thus, c-Rel is a myeloid checkpoint that can be targeted for treating cancer.
Identifiants
pubmed: 33458695
doi: 10.1038/s43018-020-0061-3
pmc: PMC7808269
mid: NIHMS1647910
pii: 10.1038/s43018-020-0061-3
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Pagination
507-517Subventions
Organisme : NIAID NIH HHS
ID : R01 AI121166
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007780
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI152195
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI099216
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI136945
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI143676
Pays : United States
Commentaires et corrections
Type : CommentIn
Déclaration de conflit d'intérêts
Competing Interests: YHC and RM are inventors of the following patent that describes the c-Rel inhibitor used in this study: Chen, Y. H., R. Murali, J. Sun: REL INHIBITORS AND METHODS OF USE THEREOF. USA Patent Number US8609730B2, 2013. YHC is a member of the advisory board of Amshenn Co., and Binde Co.
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