Zisakis Athanasios, Piperi Christina, Themistocleous Marios S, Korkolopoulou Penelope, Boviatsis Efstathios I, Sakas Damianos E, Patsouris Efstratios, Lea Robert W, Kalofoutis Anastasios
Laboratory of Biological Chemistry, University of Athens Medical School, M. Asias 75, Goudi 11527, Athens, Greece.
Cytokine. 2007 Aug;39(2):99-105. doi: 10.1016/j.cyto.2007.05.012. Epub 2007 Aug 13.
Malignant gliomas are the most common primary brain tumours of both children and adults. The unique aspects of their biology and anatomic site render them refractory to conventional therapeutic strategies such as surgery and chemotherapy. Significant attention has been given, recently, to immunotherapy which, although promising in preclinical studies, has not yet enhanced the survival of patients with glioblastomas.
To further understand the immunobiology of glioblastomas in clinical settings, we examined the secretion of four main cytokines in the peripheral blood and in primary cell cultures of 33 human glioblastoma patients. An ELISPOT methodology was used for the first time to examine Th1, and Th2 cytokine secretion from both peripheral lymphocytes and glioma tumour cells.
Th1 cytokines (tumour necrosis factor (TNF-alpha), interferon (IFN-gamma) were markedly reduced compared to control levels (P=0.01 and P<0.001, respectively), whereas in contrast, Th2 (interleukin (IL)-4 and IL-10) were strongly expressed in both peripheral lymphocytes and glioma cell cultures (P=0.05 and P<0.001, respectively).
This pattern indicates an 'immunosuppressive status' in glioblastomas which is related to their origination and the evasion of glioma cells from immune surveillance and could account for the failure of immunotherapy in such tumours. Furthermore, ELISPOT methodology can be used for monitoring of cytokine secretion from tumour cells, in addition to the well-established peripheral cytokine secretion.
恶性胶质瘤是儿童和成人中最常见的原发性脑肿瘤。其生物学特性和解剖部位的独特性使得它们对手术和化疗等传统治疗策略具有抗性。最近，免疫疗法受到了极大关注，尽管在临床前研究中有前景，但尚未提高胶质母细胞瘤患者的生存率。
为了进一步了解临床环境中胶质母细胞瘤的免疫生物学，我们检测了33例人类胶质母细胞瘤患者外周血和原代细胞培养物中四种主要细胞因子的分泌情况。首次使用ELISPOT方法检测外周淋巴细胞和胶质瘤肿瘤细胞中Th1和Th2细胞因子的分泌。
与对照水平相比，Th1细胞因子（肿瘤坏死因子（TNF-α）、干扰素（IFN-γ））明显降低（分别为P = 0.01和P < 0.001），而相比之下，Th2（白细胞介素（IL）-4和IL-10）在周淋巴细胞和胶质瘤细胞培养物中均强烈表达（分别为P = 0.05和P < 0.001）。
这种模式表明胶质母细胞瘤中存在“免疫抑制状态”，这与其起源以及胶质瘤细胞逃避免疫监视有关，并且可以解释此类肿瘤免疫治疗的失败。此外，除了已确立的外周细胞因子分泌检测外，ELISPOT方法还可用于监测肿瘤细胞的细胞因子分泌。
