Open Accessc-Rel is a myeloid checkpoint for cancer immunotherapy
Author(s) -
Ting Li,
Xinyuan Li,
Ali Zamani,
Wei Wang,
Chin-Nien Lee,
Mingyue Li,
George Luo,
Emily Eiler,
Honghong Sun,
Sankar Ghosh,
Jian Jin,
Ramachandran Murali,
Qingguo Ruan,
Weiyun Shi,
Youhai H. Chen
Publication year - 2020
Publication title -
nature cancer
Language(s) - English
Resource type - Journals
ISSN - 2662-1347
DOI - 10.1038/s43018-020-0061-3
Subject(s) - cancer research , myeloid , cancer immunotherapy , immunotherapy , cancer , cancer cell , biology , immunology , medicine , genetics
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.