Quirk Kendel, Ganapathy-Kanniappan Shanmugasundaram
Division of Interventional Radiology, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Front Pharmacol. 2017 Oct 17;8:732. doi: 10.3389/fphar.2017.00732. eCollection 2017.
Natural killer (NK) cells are critical effectors of the immune system. NK cells recognize unhealthy cells by specific ligands [e.g., MHC- class I chain related protein A or B (MIC-A/B)] for further elimination by cytotoxicity. Paradoxically, cancer cells down-regulate MIC-A/B and evade NK cell's anticancer activity. Recent data indicate that cellular-stress induces MIC-A/B, leading to enhanced sensitivity of cancer cells to NK cell-mediated cytotoxicity. In this article, we hypothesize that current chemotherapeutics at sub-lethal, non-toxic dose may promote cellular-stress and up-regulate the expression of MIC-A/B ligands to augment cancer's sensitivity to NK cell-mediated cytotoxicity. Preliminary data from two human breast cancer cell lines, MDA-MB-231 and T47D treated with clinically relevant therapeutics such as doxorubicin, paclitaxel and methotrexate support the hypothesis. The goal of this is to underscore the prospects of current chemotherapeutics in NK cell immunotherapy, and discuss potential challenges and opportunities to improve cancer therapy.
自然杀伤（NK）细胞是免疫系统的关键效应细胞。NK细胞通过特定配体（如MHC-I类链相关蛋白A或B（MIC-A/B））识别不健康细胞，进而通过细胞毒性作用将其清除。矛盾的是，癌细胞会下调MIC-A/B，逃避NK细胞的抗癌活性。近期数据表明，细胞应激会诱导MIC-A/B表达，从而增强癌细胞对NK细胞介导的细胞毒性的敏感性。在本文中，我们推测当前亚致死、无毒剂量的化疗药物可能会促进细胞应激并上调MIC-A/B配体的表达，以增强癌症对NK细胞介导的细胞毒性的敏感性。来自两种人乳腺癌细胞系MDA-MB-231和T47D，用阿霉素、紫杉醇和甲氨蝶呤等临床相关治疗药物处理后的初步数据支持了这一假设。本文的目的是强调当前化疗药物在NK细胞免疫治疗中的前景，并讨论改善癌症治疗的潜在挑战和机遇。
