Discipline of Biosciences and Biomedical Engineering (BSBE), Indian Institute of Technology Indore (IITI), Simrol, 453552, India.
Department of Pathology, Immunology and Laboratory Medicine, Rutgers University-New Jersey Medical School, 185 South Orange Avenue, Newark, NJ, 07103, USA.
Inflamm Res. 2020 May;69(5):435-451. doi: 10.1007/s00011-020-01318-0. Epub 2020 Mar 11.
This review focuses on exosomes derived from various cancer cells. The review discusses the possibility of differentiating macrophages in alternatively activated anti-inflammatory pro-tumorigenic M2 macrophage phenotypes and classically activated pro-inflammatory, anti-tumorigenic M1 macrophage phenotypes in the tumor microenvironment (TME). The review is divided into two main parts, as follows: (1) role of exosomes in alternatively activating M2-like macrophages-breast cancer-derived exosomes, hepatocellular carcinoma (HCC) cell-derived exosomes, lung cancer-derived exosomes, prostate cancer-derived exosomes, Oral squamous cell carcinoma (OSCC)-derived exosomes, epithelial ovarian cancer (EOC)-derived exosomes, Glioblastoma (GBM) cell-derived exosomes, and colorectal cancer-derived exosomes, (2) role of exosomes in classically activating M1-like macrophages, oral squamous cell carcinoma-derived exosomes, breast cancer-derived exosomes, Pancreatic-cancer derived modified exosomes, and colorectal cancer-derived exosomes, and (3) exosomes and antibody-dependent cellular cytotoxicity (ADCC). This review addresses the following subjects: (1) crosstalk between cancer-derived exosomes and recipient macrophages, (2) the role of cancer-derived exosome payload(s) in modulating macrophage fate of differentiation, and (3) intracellular signaling mechanisms in macrophages regarding the exosome's payload(s) upon its uptake and regulation of the TME.
Under the electron microscope, nanoscale exosomes appear as specialized membranous vesicles that emerge from the endocytic cellular compartments. Exosomes harbor proteins, growth factors, cytokines, lipids, miRNA, mRNA, and DNAs. Exosomes are released by many cell types, including reticulocytes, dendritic cells, B-lymphocytes, platelets, mast cells, and tumor cells. It is becoming clear that exosomes can impinge upon signal transduction pathways, serve as a mediator of signaling crosstalk, thereby regulating cell-to-cell wireless communications.
Based on the vesicular cargo, the molecular constituents, the exosomes have the potential to change the fate of macrophage phenotypes, either M1, classically activated macrophages, or M2, alternatively activated macrophages. In this review, we discuss and describe the ability of tumor-derived exosomes in the mechanism of macrophage activation and polarization.
本综述重点关注源自各种癌细胞的外泌体。本文讨论了在外泌体的作用下，肿瘤微环境（TME）中的巨噬细胞是否有可能分化为具有不同功能的两种表型：M2 型（替代激活的抗炎型、促肿瘤生成型）和 M1 型（经典激活的促炎型、抗肿瘤型）。本文分为两个主要部分，如下所述：（1）外泌体在替代激活 M2 样巨噬细胞中的作用-乳腺癌来源的外泌体、肝细胞癌（HCC）细胞来源的外泌体、肺癌来源的外泌体、前列腺癌来源的外泌体、口腔鳞状细胞癌（OSCC）来源的外泌体、上皮性卵巢癌（EOC）来源的外泌体、胶质母细胞瘤（GBM）细胞来源的外泌体和结直肠癌来源的外泌体；（2）外泌体在经典激活 M1 样巨噬细胞中的作用-口腔鳞状细胞癌来源的外泌体、乳腺癌来源的外泌体、胰腺癌衍生的修饰外泌体和结直肠癌来源的外泌体；（3）外泌体和抗体依赖的细胞毒性（ADCC）。本文讨论了以下主题：（1）肿瘤来源的外泌体与受体巨噬细胞之间的相互作用；（2）肿瘤来源的外泌体有效载荷在调节巨噬细胞分化命运中的作用；（3）巨噬细胞摄取外泌体及其对细胞内信号转导的调节，以及外泌体有效载荷对肿瘤微环境的调节。
在电子显微镜下，纳米级外泌体呈现出特殊的膜状囊泡，这些囊泡从细胞内的内吞隔室中出现。外泌体包含蛋白质、生长因子、细胞因子、脂质、miRNA、mRNA 和 DNA。许多细胞类型都会释放外泌体，包括网织红细胞、树突状细胞、B 淋巴细胞、血小板、肥大细胞和肿瘤细胞。现在已经清楚的是，外泌体可以影响信号转导途径，充当信号串扰的介质，从而调节细胞间的无线通信。
基于囊泡的货物、分子成分，外泌体有可能改变巨噬细胞表型的命运，无论是 M1 型（经典激活的促炎型、抗肿瘤型）还是 M2 型（替代激活的抗炎型、促肿瘤生成型）。在本综述中，我们讨论并描述了肿瘤来源的外泌体在巨噬细胞激活和极化机制中的作用。
