Dietrich Pierre-Yves, Dutoit Valérie, Walker Paul R
From the Center of Oncology, Geneva University Hospitals, Geneva, Switzerland.
Am Soc Clin Oncol Educ Book. 2014:51-9. doi: 10.14694/EdBook_AM.2014.34.51.
There is now evidence that the rules established for tumor immunology and immunotherapy in general are relevant for brain tumors. Treatment strategies explored have mainly involved vaccines using either tumor cells or components, and vaccines with defined synthetic peptides. This latter approach offers the advantage to select well-characterized antigens with selective or preferential expression on glioma. This is a prerequisite because collateral damage to the brain is not allowed. A second strategy which is reaching clinical trials is T cell therapy using the patients' own lymphocytes engineered to become tumor reactive. Tumor specificity can be conferred by forced expression of either a high-avidity T cell receptor or an antitumor antibody (the latter cells are called chimeric antigen receptors). An advantage of T cell engineering is the possibility to modify the cells to augment cellular activation, in vivo persistence and resistance to the tumor immunosuppressive milieu. A direct targeting of the hostile glioma microenvironment will additionally be required for achieving potent immunotherapy and various trials are assessing this issue. Finally, combining immunotherapy with immune checkpoint inhibitors and chemotherapy must be explored within rigorous clinical trials that favor constant interactions between the bench and bedside. Regarding immunotherapy for glioma patients, what was an unrealistic dream a decade ago is today a credible prospect.
目前有证据表明，一般为肿瘤免疫学和免疫疗法制定的规则适用于脑肿瘤。所探索的治疗策略主要包括使用肿瘤细胞或其成分的疫苗，以及含有特定合成肽的疫苗。后一种方法具有优势，能够选择在胶质瘤上有选择性或优先表达的、特征明确的抗原。这是一个先决条件，因为不允许对大脑造成附带损害。正在进入临床试验的第二种策略是T细胞疗法，使用经改造使其具有肿瘤反应性的患者自身淋巴细胞。可以通过强制表达高亲和力T细胞受体或抗肿瘤抗体（后一种细胞称为嵌合抗原受体）来赋予肿瘤特异性。T细胞工程的一个优点是有可能对细胞进行改造，以增强细胞活化、体内持久性以及对肿瘤免疫抑制环境的抗性。为了实现有效的免疫疗法，还需要直接靶向恶性胶质瘤微环境，并且各种试验正在评估这一问题。最后，必须在严格的临床试验中探索将免疫疗法与免疫检查点抑制剂和化疗相结合的方法，这些试验有利于基础研究与临床实践之间的持续互动。对于胶质瘤患者的免疫疗法而言，十年前还是不切实际的梦想，如今已成为可信的前景。
