Eder Katalin, Kalman Bernadette
Department of Molecular Pathology, Markusovszky University Teaching Hospital, Markusovszky Street 5, Szombathely, 9700, Hungary.
University of Pecs, Pecs, Hungary.
Neuromolecular Med. 2015 Dec;17(4):335-52. doi: 10.1007/s12017-015-8362-x. Epub 2015 Jul 30.
Glioblastoma is the most common intracranial malignancy that constitutes about 50 % of all gliomas. Despite aggressive, multimodal therapy consisting of surgery, radiation, and chemotherapy, the outcome of patients with glioblastoma remains poor with 5-year survival rates of <10 %. Resistance to conventional therapies is most likely caused by several factors. Alterations in the functions of local immune mediators may represent a critical contributor to this resistance. The tumor microenvironment contains innate and adaptive immune cells in addition to the cancer cells and their surrounding stroma. These various cells communicate with each other by means of direct cell-cell contact or by soluble factors including cytokines and chemokines, and act in autocrine and paracrine manners to modulate tumor growth. There are dynamic interactions among the local immune elements and the tumor cells, where primarily the protective immune cells attempt to overcome the malignant cells. However, by developing somatic mutations and epigenetic modifications, the glioblastoma tumor cells acquire the capability of counteracting the local immune responses, and even exploit the immune cells and products for their own growth benefits. In this review, we survey those immune mechanisms that likely contribute to glioblastoma pathogenesis and may serve as a basis for novel treatment strategies.
胶质母细胞瘤是最常见的颅内恶性肿瘤,约占所有胶质瘤的50%。尽管采用了包括手术、放疗和化疗在内的积极多模式治疗,但胶质母细胞瘤患者的预后仍然很差,5年生存率低于10%。对传统疗法的耐药性很可能是由多种因素引起的。局部免疫介质功能的改变可能是导致这种耐药性的关键因素。肿瘤微环境除了包含癌细胞及其周围的基质外,还含有先天免疫细胞和适应性免疫细胞。这些不同的细胞通过直接的细胞间接触或通过包括细胞因子和趋化因子在内的可溶性因子相互交流,并以自分泌和旁分泌的方式调节肿瘤生长。局部免疫元件与肿瘤细胞之间存在动态相互作用,其中主要是保护性免疫细胞试图战胜恶性细胞。然而,通过发生体细胞突变和表观遗传修饰,胶质母细胞瘤肿瘤细胞获得了对抗局部免疫反应的能力,甚至利用免疫细胞和产物来促进自身生长。在这篇综述中,我们探讨了那些可能导致胶质母细胞瘤发病机制并可能作为新治疗策略基础的免疫机制。