Pries Ralph, Wulff Sandra, Kesselring Rebecca, Börngen Kirsten, Xie Lei, Wollenberg Barbara
Department of Otorhinolaryngology, University of Schleswig-Holstein Campus Lübeck, D-23538 Lübeck, Germany.
Int J Oncol. 2008 Nov;33(5):993-1000.
Natural killer (NK) cells play a crucial role in innate immunity as effectors against tumor and pathogen-infected cells. NK-mediated host defense against tumor cells is strongly impaired in patients with head and neck squamous cell carcinoma (HNSCC). Tumor secretion of various immune suppressive mediators contributes to massively compromised immune functions. Herein we demonstrate that NK cell cytotoxicity against tumor cells of HNSCC can be efficiently stimulated by single-stranded immunostimulatory RNA (ss-isRNA). Stimulation with ss-isRNA results in an increased production of interferon-gamma and effector proteins perforin and granzyme B. Our investigations revealed that supernatants of permanent HNSCC cell lines negatively affect the ss-isRNA-triggered stimulation of cytolytic NK cell functions. Stimulation of cytotoxicity requires toll-like receptor 7 (TLR7). Increased expression of NK cell TLR7 was shown in response to ss-isRNA. These results suggest ss-isRNA as a potential immunostimulatory tool of human NK cells against HNSCC.
自然杀伤（NK）细胞作为针对肿瘤细胞和病原体感染细胞的效应器，在先天免疫中发挥着关键作用。在头颈部鳞状细胞癌（HNSCC）患者中，NK介导的宿主对肿瘤细胞的防御能力严重受损。肿瘤分泌的各种免疫抑制介质导致免疫功能大幅受损。在此，我们证明单链免疫刺激RNA（ss-isRNA）可有效刺激NK细胞对HNSCC肿瘤细胞的细胞毒性。用ss-isRNA刺激可导致γ干扰素以及效应蛋白穿孔素和颗粒酶B的产生增加。我们的研究表明，HNSCC永久细胞系的上清液会对ss-isRNA触发的溶细胞性NK细胞功能刺激产生负面影响。细胞毒性的刺激需要Toll样受体7（TLR7）。结果显示，响应ss-isRNA，NK细胞TLR7的表达增加。这些结果表明，ss-isRNA是人类NK细胞对抗HNSCC的一种潜在免疫刺激工具。
