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

DOI
https://doi.org/10.1038/s41467-022-31764-9
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 18

Abstract

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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.