Chung JS, Lee S, Yoo YD

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Chung JS, Lee S, Yoo YD. 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. strong class=”kwd-title” Keywords: glioblastoma, immunotherapy, Romo1, macrophages, immune response INTRODUCTION Glioma is the most common brain neoplasms among adult worldwide, and about 50% of patients present with the most aggressive form of the disease, glioblastoma [1]. Common therapies for glioblastoma include medical procedures, radiotherapy, and concomitant temozolomide-based chemotherapy, but improvements remain limited in the survival outcomes of patients [1]. Over the past decade, immunotherapy represented by PD-1/L1 immune checkpoint blockade has achieved remarkable success in several tumor types like advanced melanoma [2C5] and non-small-cell lung malignancy (NSCLC) [6, 7], and has attracted considerable interest from your glioblastoma community. However, a recent clinical trial of PD-1 inhibitors in recurrent glioblastoma showed that only a small part of patients demonstrated long-term responses [8], probably due to the alterations of molecular signatures that regulate the immune tolerance within tumor microenvironment [9]. Reactive oxygen species (ROS) modulator 1 (Romo1) is a mitochondrial membrane protein that is thought to be involved in mitochondrial ROS production redox sensing in mitochondrial dynamics [10, 11]. Romo1 was considered to participate in tumor growth and invasiveness [12C14]. A recent clinical study reported that this overexpression of Romo1 predicted unfavorable prognosis and lymphatic metastasis in NLCLC [15], but the role of Romo1 in tumorigenesis still remain unclear. In our preliminary study, we found that the high expression of Romo1 is usually associated with the poor prognosis of glioblastoma patients and that Romo1 is highly expressed in macrophages. Through the orthotopic glioblastoma mouse model, we also found that the overexpression of Romo1 in bone marrow cells inhibited the Aspirin immune response within tumor microenvironment, implicating that Romo1 may also participate in the immune tolerance of tumor. Aspirin These results motivated us to characterize the role of Romo1 in macrophages and the progression of glioblastoma. RESULTS The high expression of Romo1 is usually associated Aspirin with Rabbit Polyclonal to Collagen XII alpha1 the poor prognosis of glioblastoma patients To reveal the relationship between Romo1 expression and the progression of glioblastoma, we extracted the mRNA levels of Romo1 in the tumor tissues of glioblastoma patients with RNA-Seq data (n=156) from your Glioblastoma Multiforme dataset of TCGA database. We found that the mRNA levels in glioblastoma samples were significantly higher than the mRNA levels of Romo1 in the normal brain samples (n=5, p 0.01, Physique 1A). Further we asked whether the expression levels influence the prognosis of the glioblastoma patients. We analyzed the survival information of the patients with the mRNA microarray data (n=511) from your Glioblastoma Multiforme dataset of TCGA database, and found that the overall survival of the patients with high expression of Romo1 (n=127, top 25% in rank) was significantly lower than the patients with low expression of Romo1 (n=384, bottom 75% in rank, p 0.0001, Figure 1B), indicating that the high expression of Romo1 may participate in the progression of glioblastoma. Open in a separate window Physique 1 The high expression of Romo1 is usually associated with the poor prognosis of glioblastoma patients. (A) The mRNA levels of Romo1 in the tumor tissues of glioblastoma patients (n=156) and the healthy brain tissues (n=5) were compared. The mRNA levels were compared between the samples with RNA-Seq data published in TCGA database. (B) The survival curves of the glioblastoma patients with high expression (n=127) and low expression (n=384) of Romo1. The mRNA levels were compared between the samples with mRNA microarray data published in TCGA database. (C) The protein levels of Romo1 in Aspirin different forms of patient-derived immune cells were detected by western blotting. (D) The mRNA levels of Romo1 in different forms of patient-derived immune cells were analyzed by RT-qPCR. (E) The tissue sections of the paratumors and.