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Necroptosis in the sarcoma immune microenvironment: From biology to therapy
Huali Ye1, Minxun Lu1, Chongqi Tu1
1Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, China.
Abstract:
Apoptosis resistance remains a major obstacle to treatment failure in sarcoma. Necroptosis is a caspase-independent programmed cell death, investigated as a novel strategy to eradicate anti-apoptotic tumor cells. The process is mediated by the receptor-interacting proteins kinase family and mixed lineage kinase domain-like proteins, which is morphologically similar to necrosis. Recent studies suggest that necroptosis in the tumor microenvironment has pro- or anti-tumor effects on immune response and cancer development. Necroptosis-related molecules display a remarkable value in prognosis prediction and therapeutic response evaluation of sarcoma. Furthermore, the induction of tumor necroptosis has been explored as a feasible therapeutic strategy against sarcoma and to synergize with immunotherapy. This review discusses the dual roles of necroptosis in the immune microenvironment and tumor progression, and explores the potential of necroptosis as a new target for sarcoma treatment.
Insights
Necroptosis, a programmed cell death, offers a new strategy against apoptosis-resistant sarcoma. This cell death pathway shows potential for sarcoma treatment and combination with immunotherapy.
Area of Science:
- Oncology
- Immunology
- Cell Death Research
Background:
- Apoptosis resistance is a key challenge in sarcoma treatment failure.
- Necroptosis, a distinct programmed cell death, is explored as an alternative to overcome resistance.
- The role of necroptosis in the tumor microenvironment's immune response and cancer development is under investigation.
Purpose of the Study:
- To review the dual roles of necroptosis in the tumor immune microenvironment and sarcoma progression.
- To explore the therapeutic potential of targeting necroptosis in sarcoma.
- To evaluate necroptosis as a strategy to synergize with immunotherapy for sarcoma treatment.
Main Methods:
- Literature review of necroptosis mechanisms and its role in cancer.
- Analysis of necroptosis-related molecules in sarcoma prognosis and treatment response.
- Exploration of necroptosis induction as a therapeutic strategy.
Main Results:
- Necroptosis is mediated by RIPK and MLKL proteins and resembles necrosis morphologically.
- Necroptosis can exert either pro- or anti-tumor effects within the tumor microenvironment.
- Necroptosis-associated molecules are valuable for predicting sarcoma prognosis and treatment outcomes.
Conclusions:
- Necroptosis presents a promising therapeutic target for overcoming apoptosis resistance in sarcoma.
- Inducing necroptosis may serve as a viable strategy for sarcoma treatment, potentially enhancing immunotherapy efficacy.
- Further research into necroptosis modulation could lead to novel sarcoma treatment approaches.
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