Intratumoral CD56bright natural killer cells are associated with improved survival in bladder cancer.
Intratumoral CD56bright natural killer cells are associated with improved survival in bladder cancer.
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DOI：
10.18632/oncotarget.26362
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发表时间：
2018-11-23
期刊：
影响因子：
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通讯作者：
Svatek, Robert S
中科院分区：
文献类型：
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作者：
Mukherjee, Neelam;Ji, Niannian;Svatek, Robert S
背景技术背景：自然杀伤（NK）细胞以非MHC限制性方式有效杀死肿瘤，是癌症治疗的新兴靶点，但其在膀胱癌（BC）中的重要性定义不清。NK细胞通常基于CD56的相对表面表达被细分为群体。两个主要的亚群是CD56bright和CD56dim NK cells.METHODS：肿瘤内淋巴细胞的患病率进行了检查，通过流式细胞术分析膀胱组织从当地队列的患者与非侵入性和侵入性BC（n=28）。采用考克斯回归分析方法对50例BC患者的NK细胞亚群与癌症特异性生存期（CSS）和总生存期（OS）的关系进行了研究。采用流式细胞术（FACS）检测膀胱肿瘤内淋巴细胞中CD56 NK细胞亚群的功能，包括细胞因子的产生和体外细胞毒活性。肿瘤内CD56bright NK细胞与其CD56dim对应物相比，细胞因子产生和细胞毒性增加，并与CSS和OS改善相关，与病理肿瘤分期无关。另一方面，CD56dim NK细胞与改善的结果无关，但与较高的病理stage.CONCLUSIONS：NK细胞是常见的肿瘤内淋巴细胞在BC。膀胱肿瘤内的CD56bright NK细胞是功能性的和与肿瘤相关的，而CD56dim NK细胞是功能失调的，在更高阶段的肿瘤中普遍存在。因此，CD56bright NK细胞是BC中有希望的靶点。
BACKGROUND: Natural killer (NK) cells are effective at killing tumors in a non-MHC restricted manner and are emerging targets for cancer therapy but their importance in bladder cancer (BC) is poorly defined. NK cells are commonly subdivided into populations based on relative surface expression of CD56. Two major subsets are CD56bright and CD56dim NK cells.METHODS: The prevalence of intratumoral lymphocytes was examined via flow cytometric analysis of bladder tissue from a local cohort of patients with non-invasive and invasive BC (n=28). The association of NK cell subsets with cancer-specific survival (CSS) and overall survival (OS) was examined in 50 patients with BC using Cox regression. Fluorescence-activated cell sorting (FACS) of intratumoral lymphocytes isolated CD56 NK cell subsets were used for examination of function, including cytokine production and in vitro cytotoxicity.RESULTS: NK cells predominated among bladder intratumoral lymphocytes. Intratumoral CD56bright NK cells showed increased cytokine production and cytotoxicity compared to their CD56dim counterparts and were associated with improved CSS and OS independent of pathologic tumor stage. On the other hand, CD56dim NK cells were not associated with improved outcomes but were associated with higher pathologic stage.CONCLUSIONS: NK cells are frequent among intratumoral lymphocytes in BC. Bladder intratumoral CD56bright NK cells are functional and prognostically relevant whereas CD56dim NK cells are dysfunctional and prevalent in higher stage tumors. Thus, CD56bright NK cells are promising targets in BC.