Romo1 is involved in the immune response of glioblastoma by regulating the function of macrophages
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Published on: October 20, 2016
Guan Sun1, Ying Cao2, Chunfa Qian3
1Department of Neurosurgery, Yancheng City No.1 People's Hospital, The Fourth Affiliated Hospital of Nantong University, Yancheng, PR China.
Abstract:
Reactive oxygen species (ROS) modulator 1 (Romo1) is a mitochondrial membrane protein that is essential for the regulation of mitochondrial ROS production and redox sensing. Although the physiological functions of Romo1 have been studied for the past few years, the role of Romo1 in cancer remained unclear. In this study, we found that the high expression of Romo1 is associated with the poor prognosis of glioblastoma patients. Further study revealed that Romo1 is highly expressed in macrophages, indicating that the overexpression of Romo1 may participate in the function of macrophages and contribute to the progression of glioblastoma. Through the glioblastoma mouse model, we found that the overexpression of Romo1 in bone marrow cells significantly inhibited the immune response within tumor microenvironment, and that the overexpression of Romo1 resulted in the M2 polarization of bone marrow derived macrophages (BMDMs) through mTORC1 signaling pathway. In addition, the inhibition of Romo1 combining with anti-PD-1 immunotherapy significantly improved the survival outcome of glioblastoma in mouse model. Collectively, our study highlights the important role of Romo1 in immune response especially the function of macrophages, and implicates it as a potential target of immunotherapy for glioblastoma.
Insights
Reactive oxygen species modulator 1 (Romo1) overexpression in glioblastoma hinders anti-tumor immunity by promoting M2 macrophage polarization. Inhibiting Romo1 combined with immunotherapy improves survival, suggesting Romo1 as a therapeutic target.
Area of Science:
- * Oncology
- * Immunology
- * Cell Biology
Background:
- * Reactive oxygen species (ROS) modulator 1 (Romo1) is a mitochondrial protein regulating ROS production and redox sensing.
- * The role of Romo1 in cancer, particularly glioblastoma, has been largely unexplored.
- * Romo1's function in macrophages and its impact on the tumor microenvironment are not well understood.
Purpose of the Study:
- * To investigate the role of Romo1 in glioblastoma progression and patient prognosis.
- * To elucidate the mechanism by which Romo1 influences the tumor immune microenvironment.
- * To evaluate Romo1 as a potential therapeutic target for glioblastoma immunotherapy.
Main Methods:
- * Analysis of Romo1 expression in glioblastoma patient samples and correlation with prognosis.
- * Investigation of Romo1 expression in macrophages and its effect on bone marrow-derived macrophages (BMDMs) polarization.
- * Utilizing a glioblastoma mouse model to assess the impact of Romo1 overexpression on immune response and therapeutic efficacy of Romo1 inhibition combined with anti-PD-1 immunotherapy.
Main Results:
- * High Romo1 expression correlates with poor glioblastoma prognosis.
- * Romo1 is highly expressed in macrophages and its overexpression inhibits anti-tumor immune responses within the tumor microenvironment.
- * Overexpression of Romo1 promotes M2 polarization of BMDMs via the mTORC1 signaling pathway.
- * Inhibition of Romo1 combined with anti-PD-1 immunotherapy significantly improves survival in a glioblastoma mouse model.
Conclusions:
- * Romo1 plays a critical role in modulating immune responses within the glioblastoma tumor microenvironment, particularly through macrophage polarization.
- * Romo1 is implicated as a key factor in glioblastoma progression and immune evasion.
- * Targeting Romo1 represents a promising strategy for enhancing the efficacy of immunotherapy in glioblastoma treatment.
