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:Dynamic changes in peripheral B and NK cells reflect treatment response in breast cancer subtypes.
Dynamic changes in peripheral B and NK cells reflect treatment response in breast cancer subtypes.
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外周血 B 细胞和 NK 细胞百分比在治疗期间呈现动态且部分协调的变化。以 B 细胞百分比降低和 NK 细胞百分比升高为特征的模式可能与治疗反应相关。这些发现属于探索性和假设生成性质,在潜在临床应用之前,需要在前瞻性、特征明确的队列中进一步验证。
免疫微环境在乳腺癌进展和治疗反应中起着关键作用。在循环免疫细胞中,B细胞和自然杀伤(NK)细胞在肿瘤动态中显示出不同且可能相反的作用。然而,外周血B细胞和NK细胞百分比的动态变化是否与不同分子亚型乳腺癌的治疗反应相关仍不清楚。
收集乳腺癌患者在标准化亚型指导治疗(根据临床指南进行化疗、抗HER2治疗和/或内分泌治疗)前后的外周血样本。采用流式细胞术定量CD45+淋巴细胞中B细胞和NK细胞的百分比。采用Spearman秩相关评估B细胞与NK细胞百分比之间的关联。采用Wilcoxon符号秩检验进行配对比较。根据RECIST标准,治疗疗效定义为客观缓解率(完全缓解+部分缓解,CR+PR)。治疗后B细胞百分比下降且NK细胞百分比升高的患者被定义为B-NK组。
亚型A(--组)与其他亚型相比,B细胞百分比显著更高,NK细胞百分比显著更低(P < 0.05)。在整个队列及大多数亚型中,观察到B细胞与NK细胞百分比之间呈显著负相关。在亚型A中,治疗后B细胞百分比显著下降(P < 0.05),而NK细胞百分比则呈现变化不一。在各亚型中,被归类为B-NK组的患者相较于非B-NK患者,倾向于具有更高的客观缓解率。
The immune microenvironment plays a critical role in breast cancer progression and therapeutic response. Among circulating immune cells, B cells and natural killer (NK) cells have shown distinct and potentially opposing roles in tumor dynamics. However, whether dynamic changes in peripheral blood B- and NK-cell percentages are associated with treatment response across molecular subtypes of breast cancer remains unclear.
Peripheral blood samples were collected from breast cancer patients before and after standardized subtype-guided therapy (chemotherapy, anti-HER2 therapy, and/or endocrine therapy according to clinical guidelines). Flow cytometry was performed to quantify the percentage of B cells and NK cells within CD45 + lymphocytes. Spearman's rank correlation was used to evaluate associations between B and NK cell percentages. Paired comparisons were performed using the Wilcoxon signed-rank test. Treatment efficacy was defined as objective response rate (complete response + partial response, CR + PR) according to RECIST criteria. Patients with decreased B cell percentage and increased NK cell percentage after treatment were defined as the B-NK group.
Subtype A (-- group) exhibited significantly higher B cells percentages and lower NK cells percentages compared with other subtypes (P < 0.05). A significant negative correlation between B and NK cell percentages was observed in overall cohort and in most subtypes. In subtype A, B cell percentage significantly decreased after treatment (P < 0.05), whereas NK cell percentage showed variable changes. Patients classified into the B-NK group tended to have a higher objective response rate compared with non-B-NK patients across subtypes.
Peripheral blood B and NK cell percentages exhibit dynamic and partially coordinated changes during treatment. A pattern characterized by decreased B cell percentage and increased NK cell percentage may be associated with treatment response. These findings are exploratory and hypothesis-generating, and further validation in prospective, well characterized cohorts is required before potential clinical application.
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