Pasqualini Claudia, Rialland Fanny, Valteau-Couanet Dominique, Michon Jean, Minard-Colin Véronique
Département de cancérologie de l'enfant et de l'adolescent, Gustave-Roussy.
Service d'hématologie clinique, Nantes.
Bull Cancer. 2018 Dec;105 Suppl 1:S68-S79. doi: 10.1016/S0007-4551(18)30392-8.
New therapeutic paradigms are needed to improve the survival of children and adolescents with high-risk malignancies, and to reduce the sequelae associated with treatment. Immunotherapies, targeting tumor cells and/or the immune system to enhance existing anti-tumor immunity or induce novel anti-tumor immune responses, are becoming increasingly successful in adult oncology. Based on the results obtained with anti-ganglioside2 antibodies in neuroblastoma, rituximab in mature B malignancies, immune checkpoint inhibitors in lymphoma and especially in Hodgkin lymphoma, blinatumomab and CAR-T CD19 cells for B-cell acute lymphoblastic leukemia, immunotherapy has demonstrated irrefutable benefits in pediatric patients. However, these results are currently limited to a minority of patients and histologies. Current and ongoing trials tend to focus on a single type of immunotherapy, but it is likely that combinations of immunotherapies with different mechanisms of action or combination with other classes of anti-cancer treatments will be additives or even synergistic. The development of this new class of drugs in the treatment of pediatric cancers has multiple challenges: to better evaluate the response to treatment, to define the optimal doses and schedules, to manage immuno-mediated toxicities, to identify its specific sequelae, and, finally, to better understand the strategies of immune evasion of pediatric cancers in order to develop efficient immunotherapies.
需要新的治疗模式来提高高危恶性肿瘤儿童和青少年的生存率，并减少与治疗相关的后遗症。免疫疗法通过靶向肿瘤细胞和/或免疫系统来增强现有的抗肿瘤免疫力或诱导新的抗肿瘤免疫反应，在成人肿瘤学中越来越成功。基于抗神经节苷脂2抗体治疗神经母细胞瘤、利妥昔单抗治疗成熟B恶性肿瘤、免疫检查点抑制剂治疗淋巴瘤尤其是霍奇金淋巴瘤、双特异性T细胞衔接器和嵌合抗原受体T细胞（CAR-T）治疗B细胞急性淋巴细胞白血病所取得的结果，免疫疗法已在儿科患者中显示出无可争议的益处。然而，目前这些结果仅限于少数患者和组织学类型。当前正在进行的试验往往侧重于单一类型的免疫疗法，但不同作用机制的免疫疗法联合使用或与其他类别的抗癌治疗联合使用可能会产生相加甚至协同的效果。这类新药在儿科癌症治疗中的开发面临多重挑战：更好地评估治疗反应、确定最佳剂量和给药方案、管理免疫介导的毒性、识别其特定后遗症，以及最后，更好地理解儿科癌症的免疫逃逸策略以开发有效的免疫疗法。
