NRF2–COX2–PGE2 axis drives immune cold tumors and predicts resistance to combination immunotherapy in hepatocellular carcinoma
Tumor-intrinsic activation of the NRF2-COX2-PGE 2 axis drives immune cold TMEs and mediates Atez/Bev resistance in HCC. Targeting this pathway may enhance efficacy, and plasma PGE 2 represents a non-invasive biomarker for stratification.
Authors
- Haruhiko Takeda
- Kazuki Maesaka
- Kenta Motomura (ORCID: https://orcid.org/0000-0002-7515-099X)
- Takahiro Kodama (ORCID: https://orcid.org/0000-0002-6250-1324)
- Shunsuke Yamamoto (ORCID: https://orcid.org/0000-0002-6550-4491)
- Yuta Myojin (ORCID: https://orcid.org/0000-0003-0360-9703)
- Hideo Shindou (ORCID: https://orcid.org/0000-0002-3443-913X)
- Kazuhiro Murai (ORCID: https://orcid.org/0000-0001-8634-2922)
- Yuki Tahata (ORCID: https://orcid.org/0000-0002-9116-7054)
- Akifumi Kuwano (ORCID: https://orcid.org/0000-0001-9397-8056)
- Amaia Lujambio (ORCID: https://orcid.org/0000-0002-2798-1481)
- Akinobu Taketomi
- Hayato Hikita (ORCID: https://orcid.org/0000-0003-2488-7315)
- Tasuku Nakabori (ORCID: https://orcid.org/0000-0002-9486-850X)
- Masanori Miyazaki (ORCID: https://orcid.org/0000-0002-4989-8929)
- Tomomi Yoshida-Hashidate
- Yasutoshi Nozaki
- Kumiko Shirai
- Kazuyoshi Ohkawa
- Yuki Makino
- Atsushi Hosui
- Akira Nishio
- Satoshi Tanaka
- Tetsuo Takehara
Institutions
- Osaka Gakuin University (JP)
- Hokkaido University (JP)
- Kyoto University (JP)
- Osaka National Hospital (JP)
- National Center for Global Health and Medicine (JP)
- Osaka Rosai Hospital (JP)
- Kansai Rosai Hospital (JP)
- Osaka Hospital (JP)
- Japan Community Healthcare Organization (JP)
- Aso Iizuka Hospital (JP)
- Osaka International Cancer Institute (JP)
- The University of Tokyo (JP)
- The University of Osaka (JP)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Hepatology
- Published
- 2026-01-15
- DOI
- https://doi.org/10.1097/hep.0000000000001677
- Citations
- 1
- Primary Topic
- Ferroptosis and cancer prognosis
- Type
- article
- Field-Weighted Citation Impact
- 36.44