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Natural killer cell impairment in ovarian clear cell carcinoma.
Journal of Leukocyte Biology ( IF 3.6 ) Pub Date : 2020-08-13 , DOI: 10.1002/jlb.5ma0720-295r Ornella Patrizi 1 , Fabio Rampinelli 2 , Daniela Coltrini 1 , Silvia Pesce 3 , Simona Carlomagno 3 , Simona Sivori 3 , Andre Pascale 4 , Emanuela Marcenaro 3 , Silvia Parolini 1 , Giovanna Tabellini 1
Journal of Leukocyte Biology ( IF 3.6 ) Pub Date : 2020-08-13 , DOI: 10.1002/jlb.5ma0720-295r Ornella Patrizi 1 , Fabio Rampinelli 2 , Daniela Coltrini 1 , Silvia Pesce 3 , Simona Carlomagno 3 , Simona Sivori 3 , Andre Pascale 4 , Emanuela Marcenaro 3 , Silvia Parolini 1 , Giovanna Tabellini 1
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In the present study, we report the analysis of NK cells derived from patients suffering from a rare ovarian cancer histotype of clear cell carcinoma (OCCC) resistant to conventional chemotherapies. We analyzed the phenotype of NK cells derived from peripheral blood (PB) and peritoneal fluid (PF) and evaluated cytotoxic interactions between NK cells and autologous tumor cells (ATC) derived from patients. We provided evidence of impaired degranulation capacity of NK cells derived from patients’ PF in the presence of ATC. Analyzing tumor cell ligands recognized by NK cell receptors, we found that ATC are characterized by an HLA class I+ phenotype (although the level of HLA‐I expression varies among all patients) and by a heterogeneous expression of ligands for activating NK receptors (from normal to decreased expression of some markers). Furthermore, we observed a down‐regulation of crucial NK cell activating receptors, primarily DNAX Accessory Molecule‐1 (DNAM‐1), on tumor‐associated NK cells. Based on these results, we propose that this severe lysis defect may be due to both negative interactions between HLA‐I‐specific inhibitory NK cell receptors/HLA‐I molecules and to defective interactions between activating NK receptors and cognate ligands. In conclusion, for the first time, the phenotypic and functional properties of tumor‐associated NK cells and their ATC derived from PF of patients with advanced stage of OCCC were characterized. Taken together results indicate altered interactions between NK cells and ATC and shed light on the aggressive mechanisms of this cancer histotype. Further studies on this rare tumor will be helpful to improve and define more effective therapies.
中文翻译：
卵巢透明细胞癌中的自然杀伤细胞损伤。
在本研究中，我们报告了对患有罕见的卵巢癌组织型透明细胞癌（OCCC）的患者的NK细胞的分析，该细胞类型对常规化疗具有抗药性。我们分析了来自外周血（PB）和腹膜液（PF）的NK细胞的表型，并评估了NK细胞与源自患者的自体肿瘤细胞（ATC）之间的细胞毒性相互作用。我们提供了在存在ATC的情况下源自患者PF的NK细胞脱粒能力受损的证据。分析被NK细胞受体识别的肿瘤细胞配体后，我们发现ATC的特征是HLA I +级表型（尽管HLA-I表达水平在所有患者中都不同）和激活NK受体的配体的异质表达（从某些标志物的正常表达到降低表达）。此外，我们观察到与肿瘤相关的NK细胞上关键的NK细胞活化受体（主要是DNAX附件分子1（DNAM-1））的表达下调。根据这些结果，我们认为这种严重的裂解缺陷可能是由于HLA-1特异性抑制性NK细胞受体/ HLA-1分子之间的负性相互作用，以及活化的NK受体与同源配体之间的相互作用不良所致。总之，首次表征了晚期OCCC患者的肿瘤相关NK细胞及其源自PF的ATC的表型和功能特性。总体而言，结果表明NK细胞与ATC之间的相互作用发生了改变，并阐明了这种癌症组织型的侵袭性机制。对这种罕见肿瘤的进一步研究将有助于改善和定义更有效的疗法。
更新日期：2020-09-30
中文翻译：
卵巢透明细胞癌中的自然杀伤细胞损伤。
在本研究中，我们报告了对患有罕见的卵巢癌组织型透明细胞癌（OCCC）的患者的NK细胞的分析，该细胞类型对常规化疗具有抗药性。我们分析了来自外周血（PB）和腹膜液（PF）的NK细胞的表型，并评估了NK细胞与源自患者的自体肿瘤细胞（ATC）之间的细胞毒性相互作用。我们提供了在存在ATC的情况下源自患者PF的NK细胞脱粒能力受损的证据。分析被NK细胞受体识别的肿瘤细胞配体后，我们发现ATC的特征是HLA I +级表型（尽管HLA-I表达水平在所有患者中都不同）和激活NK受体的配体的异质表达（从某些标志物的正常表达到降低表达）。此外，我们观察到与肿瘤相关的NK细胞上关键的NK细胞活化受体（主要是DNAX附件分子1（DNAM-1））的表达下调。根据这些结果，我们认为这种严重的裂解缺陷可能是由于HLA-1特异性抑制性NK细胞受体/ HLA-1分子之间的负性相互作用，以及活化的NK受体与同源配体之间的相互作用不良所致。总之，首次表征了晚期OCCC患者的肿瘤相关NK细胞及其源自PF的ATC的表型和功能特性。总体而言，结果表明NK细胞与ATC之间的相互作用发生了改变，并阐明了这种癌症组织型的侵袭性机制。对这种罕见肿瘤的进一步研究将有助于改善和定义更有效的疗法。
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