James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Cancer Biomark. 2010;8(4-5):281-91. doi: 10.3233/CBM-2011-0211.
Tumor cells release membranous structures, defined as microvesicles or exosomes, consisting of an array of macromolecules derived from the originating cells, including proteins, lipids, and RNA. The expression of antigenic molecules recognizable by T cells originally suggested a role for these vesicles as a cell-free antigen source for anti-cancer vaccines; however, evidence demonstrates that tumor exosomes can exert a broad array of detrimental effects on the immune system - ranging from apoptosis of activated cytotoxic T cells to impairment of monocyte differentiation into dendritic cells, to induction of myeloid-suppressive cells. Immunosuppressive exosomes of tumor origin can be found in neoplastic lesions and biologic fluids from cancer patients, implying a potential role of these pathways in in vivo tumor progression and systemic paraneoplastic syndromes. Through the expression of molecules involved in angiogenesis promotion, stromal remodeling, signaling pathway activation through growth factor/receptor transfer, chemoresistance, and intercellular genetic exchange, tumor exosomes could represent a central mediator of the tumor microenvironment. Their release by tumor cells may represent the future for targeting therapeutic interventions and for development of multiplexed diagnostic biomarkers.
肿瘤细胞会释放出膜状结构，这些结构被定义为微泡或外泌体，由一系列源自原始细胞的大分子组成，包括蛋白质、脂质和 RNA。最初，抗原性分子的表达使这些囊泡被认为是无细胞抗原的来源，可用于抗癌疫苗；然而，有证据表明肿瘤外泌体可以对免疫系统产生广泛的有害影响 - 从激活的细胞毒性 T 细胞的凋亡到单核细胞分化为树突状细胞的损伤，再到诱导髓系抑制细胞。在肿瘤患者的肿瘤病变和生物液体中可以发现源自肿瘤的免疫抑制性外泌体，这表明这些途径在体内肿瘤进展和全身副肿瘤综合征中可能具有潜在作用。通过表达参与血管生成促进、基质重塑、通过生长因子/受体转移激活信号通路、化疗耐药和细胞间遗传交换的分子，肿瘤外泌体可能成为肿瘤微环境的主要介质。肿瘤细胞释放这些囊泡可能代表着未来靶向治疗干预和开发多重诊断生物标志物的方向。
