Fujioka Yuki, Nishikawa Hiroyoshi
Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center.
Rinsho Ketsueki. 2016;57(11):2346-2354. doi: 10.11406/rinketsu.57.2346.
The immune system is the body's defense against infectious organisms and other invaders including cancer cells. Cancer immunotherapy, which employs our own immune systems to attack cancer cells, is now emerging as a promising modality of cancer treatment based upon the clinical successes of immune checkpoint blockade and adoptive T cell transfer. In hematologic malignancies, clinical application of anti-PD-1 mAb and CAR (chimeric antigen receptor) T therapy is now being extensively tested in Hodgkin's disease, multiple myeloma, and CD19 acute lymphocytic leukemia. In sharp contrast to conventional anti-cancer reagents which directly kill cancer cells, cancer immunotherapy activates various types of immune effector cells to attack cancer cells. However, more than half of the treated patients showed no activation of anti-tumor CD8 killer T cells and CD4 helper T cells and failed to respond to immune therapies such as immune checkpoint blockade, even when administered in combination regimens. Thus, development of novel immunotherapies to achieve more effective activation of anti-cancer immunity and immuno-monitoring of biomarkers, allowing proper evaluation of immune responses in cancer patients in order to detect responders, are urgent issues. Additionally, we must pay attention to characteristic immunological side effects not observed following treatment with conventional anti-cancer reagents. Herein, we present a summary outline and discuss the future direction of cancer immunotherapy.
免疫系统是人体抵御感染性生物体和包括癌细胞在内的其他入侵者的防御机制。癌症免疫疗法利用我们自身的免疫系统来攻击癌细胞,基于免疫检查点阻断和过继性T细胞转移的临床成功,它正成为一种有前景的癌症治疗方式。在血液系统恶性肿瘤中,抗PD-1单克隆抗体和嵌合抗原受体(CAR)T细胞疗法的临床应用目前正在霍奇金淋巴瘤、多发性骨髓瘤和CD19急性淋巴细胞白血病中广泛测试。与直接杀死癌细胞的传统抗癌试剂形成鲜明对比的是,癌症免疫疗法激活各种类型的免疫效应细胞来攻击癌细胞。然而,超过一半的接受治疗的患者未表现出抗肿瘤CD8杀伤性T细胞和CD4辅助性T细胞的激活,并且对免疫疗法(如免疫检查点阻断)无反应,即使采用联合治疗方案也是如此。因此,开发新的免疫疗法以更有效地激活抗癌免疫并对生物标志物进行免疫监测,从而能够正确评估癌症患者的免疫反应以检测反应者,是亟待解决的问题。此外,我们必须关注传统抗癌试剂治疗后未观察到的独特免疫副作用。在此,我们给出一个总结概述并讨论癌症免疫疗法的未来方向。