Cancer Immunotherapy: Whence and Whither.
Cancer Immunotherapy: Whence and Whither.
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DOI：
10.1158/1541-7786.mcr-16-0427
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发表时间：
2017-06
期刊：
影响因子：
--
通讯作者：
Farzaneh F
中科院分区：
文献类型：
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作者：
Stambrook PJ;Maher J;Farzaneh F
目前癌症免疫治疗的概念和实践是从区分“自我”和“非自我”的经典实验以及体液免疫与细胞免疫互补的发现发展而来的。阐明生物学基础免疫检查点和配体与配体受体之间的相互作用，这些相互作用控制免疫系统将肿瘤细胞识别为外来物的能力，这导致了新策略的出现，这些策略动员免疫系统来逆转这种明显的耐受性。这些方法中的一些已经导致了新的疗法，例如使用单克隆抗体（mAb）来干扰免疫检查点。其他人已经利用分子技术来重新设计T细胞的亚群，以直接参与并杀死肿瘤细胞，特别是B细胞恶性肿瘤的肿瘤细胞。然而，在免疫疗法成为更有效的癌症治疗方法之前，还有许多挑战有待解决，还有许多障碍需要克服。包括操纵肿瘤微环境（TME）以增强T效应细胞浸润和进入肿瘤，增强肿瘤MHC表达以充分呈递肿瘤相关抗原，调节细胞因子及其潜在的不良反应，以及降低由于免疫细胞的各种形式的基因工程产生的突变而导致的继发性恶性肿瘤的风险。尽管存在这些挑战，但免疫疗法作为标准抗癌疗法的未来令人鼓舞。
The current concepts and practice of cancer immunotherapy evolved from classical experiments that distinguished "self" from "non-self" and the finding that humoral immunity is complemented by cellular immunity. Elucidation of the biology underlying immune checkpoints and interactions between ligands and ligand receptors that govern the immune system's ability to recognize tumor cells as foreign has led to the emergence of new strategies that mobilize the immune system to reverse this apparent tolerance. Some of these approaches have led to new therapies such as the use of monoclonal antibodies (mAbs) to interfere with the immune checkpoint. Others have exploited molecular technologies to re-engineer a subset of T cells to directly engage and kill tumor cells, particularly those of B cell malignancies. However, before immunotherapy can become a more effective method of cancer care, there are many challenges that remain to be addressed and hurdles to overcome. Included are manipulation of tumor microenvironment (TME) to enhance T effector cell infiltration and access to the tumor, augmentation of tumor MHC expression for adequate presentation of tumor associated antigens, regulation of cytokines and their potential adverse effects, and reduced risk of secondary malignancies as a consequence of mutations generated by the various forms of genetic engineering of immune cells. Despite these challenges, the future of immunotherapy as a standard anti-cancer therapy is encouraging.