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Updated: Aug 17, 2025
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
Ferroptosis and its interaction with tumor immune microenvironment in liver cancer
Yilan Huang1, Siwei Wang2, Aiwu Ke1
1Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China.
Abstract:
Exploring effective systemic treatments for liver cancer is still a great challenge worldwide. As a novel form of regulated cell death, ferroptosis has been paid more and more attention in the cancer research field. In recent years, targeting ferroptosis has become an encouraging strategy for liver cancer treatment. Cancer cells can be directly killed by inducing ferroptosis; in contrast, ferroptosis can also ameliorate the tumor immunosuppressive microenvironment and sensitize cancers to immunotherapy. Here, we summarize fully current progress in the iron homeostasis in the liver, the internal association between imbalanced iron homeostasis and ferroptosis in liver carcinogenesis and development, as well as ferroptosis-related regulators in liver cancer. Furthermore, we discuss thoroughly the interaction between ferroptosis and tumor immune microenvironment. Finally, we provide certainly a future insight on the potential value of ferroptosis in the immunotherapy of liver cancer.
Insights
Targeting ferroptosis, a novel cell death pathway, offers a promising strategy for liver cancer treatment by directly killing cancer cells and enhancing immunotherapy effectiveness. This approach addresses challenges in systemic treatment for liver cancer.
Area of Science:
- Oncology
- Cell Death Research
- Immunotherapy
Background:
- Liver cancer remains a significant global health challenge with limited effective systemic treatments.
- Ferroptosis, a regulated cell death pathway, is gaining attention for its potential in cancer therapy.
- Targeting ferroptosis presents a promising strategy for overcoming treatment resistance in liver cancer.
Purpose of the Study:
- To review the current understanding of iron homeostasis in the liver and its link to liver carcinogenesis.
- To explore the role of ferroptosis regulators in liver cancer development.
- To discuss the interplay between ferroptosis and the tumor immune microenvironment for potential immunotherapy applications.
Main Methods:
- Literature review of studies on iron metabolism, ferroptosis, and liver cancer.
- Analysis of the association between imbalanced iron homeostasis and ferroptosis in liver cancer.
- Examination of ferroptosis-related regulators and their impact on liver cancer.
Main Results:
- Imbalanced iron homeostasis is intrinsically linked to ferroptosis in liver carcinogenesis and progression.
- Ferroptosis induction can directly eliminate liver cancer cells.
- Ferroptosis can modulate the tumor immune microenvironment, enhancing sensitivity to immunotherapy.
Conclusions:
- Ferroptosis is a viable therapeutic strategy for liver cancer, offering dual benefits of direct tumor cell killing and immune microenvironment modulation.
- Further research into ferroptosis regulators and their interaction with the immune system holds significant potential for advancing liver cancer immunotherapy.
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