CD206 Expression in Induced Microglia-Like Cells From Peripheral Blood as a Surrogate Biomarker for the Specific Immune Microenvironment of Neurosurgical Diseases Including Glioma.

Shunya Tanaka,Nobuhiro Hata,Satoshi O Suzuki,Masahiro Mizoguchi,Kosuke Takigawa,Hideomi Hamasaki,Ryusuke Hatae,Masako Hosoi,Toru Iwaki,Noritoshi Shirouzu,Nobutaka Mukae,Koji Iihara,Takahiro A Kato,Yutaka Fujioka,Masahiro Ohgidani,Yuhei Sangatsuda,Noriaki Sagata,Shogo Inamine,Yusuke Funakoshi

doi:10.3389/fimmu.2021.670131

Shunya Tanaka, Nobuhiro Hata + Show 17 more

Open Access

https://doi.org/10.3389/fimmu.2021.670131

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Abstract

Targeting the unique glioma immune microenvironment is a promising approach in developing breakthrough immunotherapy treatments. However, recent advances in immunotherapy, including the development of immune checkpoint inhibitors, have not improved the outcomes of patients with glioma. A way of monitoring biological activity of immune cells in neural tissues affected by glioma should be developed to address this lack of sensitivity to immunotherapy. Thus, in this study, we sought to examine the feasibility of non-invasive monitoring of glioma-associated microglia/macrophages (GAM) by utilizing our previously developed induced microglia-like (iMG) cells. Primary microglia (pMG) were isolated from surgically obtained brain tissues of 22 patients with neurological diseases. iMG cells were produced from monocytes extracted from the patients’ peripheral blood. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) revealed a significant correlation of the expression levels of representative markers for M1 and M2 microglia phenotypes between pMG and the corresponding iMG cells in each patient (Spearman’s correlation coefficient = 0.5225, P <0.0001). Synchronous upregulation of CD206 expression levels was observed in most patients with glioma (6/9, 66.7%) and almost all patients with glioblastoma (4/5, 80%). Therefore, iMG cells can be used as a minimally invasive tool for monitoring the disease-related immunological state of GAM in various brain diseases, including glioma. CD206 upregulation detected in iMG cells can be used as a surrogate biomarker of glioma.

Highlights

Gliomas are tumors of the central nervous system (CNS) derived from neural tissues
Total RNA was isolated from these paired samples to investigate the expression profiles of Primary microglia (pMG) cells isolated from brain tissue and the corresponding blood-derived induced microglia-like (iMG) cells
PCR was performed to determine the expression levels of inflammationrelated genes known as representative markers for M1 microglia and macrophage phenotype (CD45, CD80, HLA-DR, tumor necrosis factor-alpha (TNF-a), IL1b, and IL-23) and M2 phenotype (CD206, CD209, CD23, BDNF, IL-10, and CCL18) (Supplementary Table S1)

Summary

Introduction

Gliomas are tumors of the central nervous system (CNS) derived from neural tissues. Among them, glioblastoma (GBM) has a highly aggressive phenotype and accounts for most gliomas. Among the recent attempts to develop multimodal treatment strategies to modify the extremely poor survival of GBM patients, immune checkpoint inhibitors were expected to bring about a paradigm shift, similar to that achieved in the treatment of other malignancies, such as melanoma [2, 3]. Clinical trials have failed to observe significant therapeutic benefits of immune checkpoint inhibitors in patients with GBM [4, 5]. Such unfavorable results may be partly due to the peculiar state of the immune system in glioma tissues and the CNS in general

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