RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Circulating Tumour Cell Numbers Correlate with Platelet Count and Circulating Lymphocyte Subsets in Men with Advanced Prostate Cancer: Data from the ExPeCT Clinical Trial (CTRIAL-IE 15-21).
Circulating Tumour Cell Numbers Correlate with Platelet Count and Circulating Lymphocyte Subsets in Men with Advanced Prostate Cancer: Data from the ExPeCT Clinical Trial (CTRIAL-IE 15-21).
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循环肿瘤细胞(CTC)与血小板的相互作用被认为会抑制自然杀伤(NK)细胞诱导的细胞裂解。本研究分析晚期前列腺癌男性患者的CTC数量与血小板计数及循环淋巴细胞数量之间的关系。ExPeCT试验61名参与者按体质指数分为超重/肥胖组(BMI≥25)和正常体重组(BMI<25),并随机分配参加或不参加为期6个月的运动项目。在随机分组时以及3个月和6个月时采集血样,通过ScreenCell过滤检测CTC,测量循环血小板计数,并对部分样本(n=29)进行流式细胞术。CTC计数与绝对淋巴细胞总数(r²=0.1709,P=0.0258)和NK细胞计数(r²=0.49,P<0.0001)呈正相关;血小板计数也与CTC计数呈正相关(r²=0.094,P=0.0001)。
在超重/肥胖组(n=123,P<0.0001)、非运动组(n=79,P=0.001)以及无血小板包裹的采血样本(n=128,P<0.0001)中也观察到相关性。流式细胞术显示,与非运动组(n=14)相比,运动组(n=15)血样中CD3+ T淋巴细胞比例较高(P=0.0003),B淋巴细胞(P=0.0264)和NK细胞(P=0.015)比例较低。这些发现提示,CTC在血管内转运过程中与凝血级联和先天免疫系统存在复杂相互作用;在转移过程的脆弱阶段,CTC可能成为有吸引力的定向治疗靶点。
Interactions between circulating tumour cells (CTCs) and platelets are thought to inhibit natural killer(NK)-cell-induced lysis.
We attempted to correlate CTC numbers in men with advanced prostate cancer with platelet counts and circulating lymphocyte numbers. Sixty-one ExPeCT trial participants, divided into overweight/obese and normal weight groups on the basis of a BMI 25 or <25, were randomized to participate or not in a six-month exercise programme. Blood samples at randomization, and at three and six months, were subjected to ScreenCell filtration, circulating platelet counts were obtained, and flow cytometry was performed on a subset of samples ( n = 29). CTC count positively correlated with absolute total lymphocyte count (r 2 = 0.
1709, p = 0. 0258) and NK-cell count (r 2 = 0. 49, p < 0. 0001). There was also a positive correlation between platelet count and CTC count (r 2 = 0. 094, p = 0. 0001). Correlation was also demonstrated within the overweight/obese group ( n = 123, p < 0. 0001), the non-exercise group ( n = 79, p = 0.
001) and blood draw samples lacking platelet cloaking ( n = 128, p < 0. 0001). By flow cytometry, blood samples from the exercise group ( n = 15) had a higher proportion of CD3+ T-lymphocytes ( p = 0. 0003) and lower proportions of B-lymphocytes ( p = 0. 0264) and NK-cells ( p = 0. 015) than the non-exercise group ( n = 14).
These findings suggest that CTCs engage in complex interactions with the coagulation cascade and innate immune system during intravascular transit, and they present an attractive target for directed therapy at a vulnerable stage in metastasis.
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