Natural Killer Cell-Based Immunotherapy against Solid Cancer

Pin Lv, Wenrui Li, Ruoyu Wang, Guojun Huang, Yi Zhu, Qiqiang Tao
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Abstract

As a kind of important innate lymphocytes in vivo, Natural killer (NK) cells have a rapid and efficient capacity to recognize and destroy tumor cells, senescent cells and virus-infected cells. In the past decades, NK cells have been widely applied in the treatment of hematological malignancies in clinic, even solid tumors. Successful results have been made against hematological malignancies (NCT00697671, NCT00990717, NCT00145626), but also a number of considerable challenges have been encountered during this period, such as poor outcomes in the treatment of solid tumors, difficult to migrate to and infiltrate into tumor sites, little functioning NK cell was seen in tumor stroma. Now we know tumor microenvironment has great influence on NK cell function, phenotype and activation, and it can finally give rise to NK cell dysfunction or/and exhaustion. Many strategies have been made to try to overcome those drawbacks. In this review, we discuss the current strategies to increase the NK cell-mediated tumor cell killing capacity and homing to the solid tumor site with the aim of heightening the clinical outcome in NK cell-based immunotherapy against solid cancer.
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基于自然杀伤细胞的实体癌免疫疗法
自然杀伤细胞(Natural killer, NK)作为体内重要的先天淋巴细胞,对肿瘤细胞、衰老细胞和病毒感染细胞具有快速有效的识别和破坏能力。近几十年来,NK细胞已广泛应用于临床血液系统恶性肿瘤甚至实体瘤的治疗。在治疗血液学恶性肿瘤(NCT00697671, NCT00990717, NCT00145626)方面已经取得了成功的结果,但在此期间也遇到了一些相当大的挑战,如实体瘤治疗效果不佳,难以迁移和浸润肿瘤部位,肿瘤基质中功能NK细胞很少。现在我们知道肿瘤微环境对NK细胞的功能、表型和活化有很大的影响,最终导致NK细胞功能障碍或衰竭。为了克服这些缺点,已经制定了许多策略。在这篇综述中,我们讨论了目前提高NK细胞介导的肿瘤细胞杀伤能力和归巢到实体瘤部位的策略,目的是提高NK细胞免疫治疗实体癌的临床效果。
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