c-Rel Is a Myeloid Checkpoint for Cancer Immunotherapy

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

doi:10.1038/s43018-020-0061-3

c-Rel Is a Myeloid Checkpoint for Cancer Immunotherapy

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

Research output: Contribution to journal › Article › peer-review

71 Scopus citations

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.

Original language	English
Pages (from-to)	507-517
Number of pages	11
Journal	Nature Cancer
Volume	1
Issue number	5
DOIs	https://doi.org/10.1038/s43018-020-0061-3
State	Published - 1 May 2020
Externally published	Yes

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title = "c-Rel Is a Myeloid Checkpoint for Cancer Immunotherapy",

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.",

author = "Ting Li and Xinyuan Li and Ali Zamani and Wei Wang and Lee, {Chin Nien} and Mingyue Li and George Luo and Emily Eiler and Honghong Sun and Sankar Ghosh and Jian Jin and Ramachandran Murali and Qingguo Ruan and Weiyun Shi and Chen, {Youhai H.}",

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AU - Li, Ting

AU - Li, Xinyuan

AU - Zamani, Ali

AU - Wang, Wei

AU - Lee, Chin Nien

AU - Li, Mingyue

AU - Luo, George

AU - Eiler, Emily

AU - Sun, Honghong

AU - Ghosh, Sankar

AU - Jin, Jian

AU - Murali, Ramachandran

AU - Ruan, Qingguo

AU - Shi, Weiyun

AU - Chen, Youhai H.

PY - 2020/5/1

Y1 - 2020/5/1

N2 - 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.

AB - 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.

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EP - 517

JO - Nature Cancer

JF - Nature Cancer

IS - 5

ER -

c-Rel Is a Myeloid Checkpoint for Cancer Immunotherapy

Abstract

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