Research Paper Volume 12, Issue 2 pp 1114—1127

Romo1 is involved in the immune response of glioblastoma by regulating the function of macrophages

Guan Sun 1, *, , Ying Cao 2, *, , Chunfa Qian 3, , Zhengqiang Wan 1, , Jian Zhu 1, , Jun Guo 1, , Lei Shi 4, ,

  • 1 Department of Neurosurgery, Yancheng City No.1 People’s Hospital, The Fourth Affiliated Hospital of Nantong University, Yancheng, PR China
  • 2 Department of Ear-Nose-Throat, The Second People's Hospital of Huai’an, Huai’an Affiliated Hospital of Xuzhou Medical University, Huai’an, PR China
  • 3 Department of Neurosurgery, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, PR China
  • 4 Department of Neurosurgery, The First People's Hospital of Kunshan Affiliated with Jiangsu University, Suzhou, Jiangsu, PR China
* Equal contribution

received: August 18, 2019 ; accepted: December 23, 2019 ; published: January 16, 2020 ;

https://doi.org/10.18632/aging.102648
How to Cite

Copyright © 2020 Sun et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.

Abbreviations

Romo1: Reactive oxygen species (ROS) modulator 1; BMDMs: Bone marrow derived macrophages; NSCLC: Non-small-cell lung cancer; DHE: Dihydroethidium; NAC: N-acetyl-cysteine; 2-NBDG: 2-Deoxy-2- [(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose; Glu: Glucose; Oli: Oligomycin; 2-DG: 2-deoxyglucose; FCCP: Carbonyl cyanide p-trifluoromethoxy-phenylhydrazone; R+A: Rotenone and Antimycin A; ECAR: Extracellular acidification rate; OCR: Oxygen consumption rate; iNOS: Inducible nitric oxide synthase.