de Micco C
Laboratoire d'anatomie pathologique et de neuropathologie, Faculté de Médecine, Marseille, France.
Bull Cancer. 1989;76(1):17-31.
Central nervous system (CNS) tumours possess special immunological features resulting from their development in an organ having a privileged immunological status. The following review gives a summary of actual data concerning their tumour-associated antigens, the immunological responses of their hosts and the mechanisms permitting them to escape from these responses. There is presently no proof of the existence of tumour-specific antigens on spontaneous glial tumours. Much progress has been made in this area with the development of monoclonal antibodies technology which mainly disclosed the profound antigenic heterogeneity of brain tumours. This heterogeneity could favour the escape of brain tumours from immunosurveillance; furthermore, it represents a major limitation to the use of monoclonal antibodies for diagnosis or therapy. Regarding the immunological responses of brain tumour patients, the main feature is a profound depression of cellular immunity creating an anergic state toward a large number of antigens. In vitro, it concerns specifically T4 helper lymphocytes: their mitogenic responses and secretion of interleukin-2 after antigenic stimuli are drastically reduced. Three phenomena have also been incriminated to explain the defect of immunosurveillance in brain tumour patients: 1) the synthesis by tumour cells of a protective mucopolysaccharidic coat, 2) the secretion by these cells of specific immunosuppressive factors related to cytokines, 3) the isolation of CNS maintained by the blood-brain barrier which regulates the circulation of immunocompetent cells between the intra- and extracerebral compartments. Currents efforts are focused on the individualization of therapy based on these biologic principles.
中枢神经系统(CNS)肿瘤因其在具有免疫特权地位的器官中发生发展而具有特殊的免疫学特征。以下综述总结了有关其肿瘤相关抗原、宿主免疫反应以及使其逃避这些反应的机制的实际数据。目前尚无证据表明自发胶质瘤存在肿瘤特异性抗原。随着单克隆抗体技术的发展,该领域取得了很大进展,该技术主要揭示了脑肿瘤深刻的抗原异质性。这种异质性可能有利于脑肿瘤逃避免疫监视;此外,它是单克隆抗体用于诊断或治疗的主要限制因素。关于脑肿瘤患者的免疫反应,主要特征是细胞免疫严重抑制,导致对大量抗原处于无反应状态。在体外,这尤其涉及T4辅助淋巴细胞:抗原刺激后它们的有丝分裂反应和白细胞介素-2的分泌大幅减少。还有三种现象被认为可以解释脑肿瘤患者免疫监视缺陷:1)肿瘤细胞合成保护性粘多糖包膜,2)这些细胞分泌与细胞因子相关的特异性免疫抑制因子,3)血脑屏障维持的中枢神经系统隔离,它调节免疫活性细胞在脑内和脑外区域之间的循环。目前的努力集中在基于这些生物学原理的个体化治疗上。