Nature Communications (Jul 2022)
Hypoxia induces HIF1α-dependent epigenetic vulnerability in triple negative breast cancer to confer immune effector dysfunction and resistance to anti-PD-1 immunotherapy
- Shijun Ma,
- Yue Zhao,
- Wee Chyan Lee,
- Li-Teng Ong,
- Puay Leng Lee,
- Zemin Jiang,
- Gokce Oguz,
- Zhitong Niu,
- Min Liu,
- Jian Yuan Goh,
- Wenyu Wang,
- Matias A. Bustos,
- Sidse Ehmsen,
- Adaikalavan Ramasamy,
- Dave S. B. Hoon,
- Henrik J. Ditzel,
- Ern Yu Tan,
- Qingfeng Chen,
- Qiang Yu
Affiliations
- Shijun Ma
- Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR)
- Yue Zhao
- Institute of Molecular and Cellular Biology, Agency for Science, Technology and Research (A*STAR)
- Wee Chyan Lee
- Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR)
- Li-Teng Ong
- Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR)
- Puay Leng Lee
- Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR)
- Zemin Jiang
- Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR)
- Gokce Oguz
- Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR)
- Zhitong Niu
- The Sixth Affiliated Hospital of Sun Yat-sen University
- Min Liu
- Institute of Molecular and Cellular Biology, Agency for Science, Technology and Research (A*STAR)
- Jian Yuan Goh
- Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR)
- Wenyu Wang
- The Sixth Affiliated Hospital of Sun Yat-sen University
- Matias A. Bustos
- Department of Translational Molecular Medicine, Saint John‘s Cancer Institute, Providence Health System
- Sidse Ehmsen
- Department of Oncology, Odense University Hospital
- Adaikalavan Ramasamy
- Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR)
- Dave S. B. Hoon
- Department of Translational Molecular Medicine, Saint John‘s Cancer Institute, Providence Health System
- Henrik J. Ditzel
- Department of Oncology, Odense University Hospital
- Ern Yu Tan
- Department of General Surgery, Tan Tock Seng Hospital
- Qingfeng Chen
- Institute of Molecular and Cellular Biology, Agency for Science, Technology and Research (A*STAR)
- Qiang Yu
- Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR)
- DOI
- https://doi.org/10.1038/s41467-022-31764-9
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 18
Abstract
Hypoxia can promote tumor escape from immune surveillance and immunotherapy. Here, the authors show that hypoxia induces T and NK cell dysfunction through HIF1α-mediated epigenetic suppression of effector gene expression, conferring resistance to anti-PD1 blockade in triple negative breast cancer models.
