Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
Curr Pharm Des. 2021;27(46):4650-4662. doi: 10.2174/1381612827666210816114003.
Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults, causing many deaths each year. The life expectancy of patients from the time of diagnosis does not exceed 15 months. Tumoral cells are generally surrounded by a bed of tumor microenvironment (TME), composed of various components such as different immune cells, stromal cells, and blood vessels. Previous studies on the treatment of this tumor have generally focused on cancerous cells and, therefore, have introduced conventional therapies for eradicating this tumor, including maximal safe surgery, chemotherapy with temozolomide (TMZ), and radiotherapy. Despite treatment with this method, tumors almost always recur, and life expectancy has not increased much. Recently, due to the discovery of the various roles of immune cells (including tumor-associated macrophages or TAMs) in the pathogenesis of this disease, the path of studies has moved towards targeting them as a treatment for glioblastoma. In this review, we aimed to investigate recent studies on the different roles of TME components, the role of TAM in the pathogenesis, and novel methods that target TAMs, including induction of TAM repolarization, inhibition of TAM-produced cytokines, and prohibition of immune system suppression induced by TAMs. In this regard, various targets, including colony-stimulating factor-1 (CSF- 1) receptors, Nuclear factor-kappa B (NF-κB), or chemokine receptor (CXCR) pathways, are investigated.
多形性胶质母细胞瘤（GBM）是成年人中最常见的恶性脑肿瘤，每年导致许多人死亡。从诊断到死亡的患者预期寿命不超过 15 个月。肿瘤细胞通常被肿瘤微环境（TME）包围，其由不同的免疫细胞、基质细胞和血管等多种成分组成。以前针对这种肿瘤的治疗研究通常集中在癌细胞上，因此引入了常规疗法来根除这种肿瘤，包括最大限度的安全手术、替莫唑胺（TMZ）化疗和放射治疗。尽管采用了这种方法，但肿瘤几乎总是会复发，患者的预期寿命并没有明显提高。最近，由于发现了免疫细胞（包括肿瘤相关巨噬细胞或 TAMs）在这种疾病发病机制中的各种作用，研究途径已经转向将它们作为治疗胶质母细胞瘤的靶点。在这篇综述中，我们旨在研究 TME 成分的不同作用、TAM 在发病机制中的作用以及靶向 TAMs 的新方法，包括诱导 TAM 重极化、抑制 TAM 产生的细胞因子以及禁止 TAMs 诱导的免疫系统抑制。在这方面，研究了各种靶点，包括集落刺激因子-1（CSF-1）受体、核因子-κB（NF-κB）或趋化因子受体（CXCR）途径。
