c-Rel Is a Myeloid Checkpoint for Cancer Immunotherapy.
Nat Cancer
; 1(5): 507-517, 2020 05.
Article
em En
| MEDLINE
| ID: mdl-33458695
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Supressoras Mieloides
/
Neoplasias
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article