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:Accumulation of CD56(+) CD16(-) Natural Killer Cells in Response to Preoperative Chemotherapy for Breast Cancer.
Accumulation of CD56(+) CD16(-) Natural Killer Cells in Response to Preoperative Chemotherapy for Breast Cancer.
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化疗前后外周血中免疫调节性 CD56 + CD16 - NK 细胞亚群的积聚,可能导致诱导抗肿瘤免疫应答的细胞因子产生。
术前化疗诱导T细胞和NK细胞抗肿瘤反应,有助乳腺肿瘤缩小。本研究评估免疫反应对疗效的贡献。
纳入2018至2023年接受术前化疗并手术的43例I至IV期乳腺癌患者。检测外周NK细胞活性,并于化疗前后测量CD4、CD8和NK细胞及亚群数量,分析其变化与疗效的关系。
单变量分析显示,较好的治疗反应与HER2阳性以及化疗后CD56阳性CD16阴性NK细胞累积相关;化疗前该亚群比例和外周NK活性较高也呈关联趋势。多变量分析中,化疗前NK活性较高与较好反应呈趋势性关联。
化疗前后外周免疫调节性CD56阳性CD16阴性NK亚群增加可能促进细胞因子产生和抗肿瘤免疫。其治疗后活化及治疗前数量较高可能有助改善乳腺癌疗效。
The activation of the antitumor immune responses of T cells and natural killer (NK) cells is important to induce breast tumor shrinkage via preoperative chemotherapy. We evaluated how antitumor immune responses contribute to the effects of such therapy.
Forty-three patients with stages I - IV breast cancer who underwent surgery between August 2018 and Jun 2023 after preoperative chemotherapy were enrolled. Peripheral natural killer (pNK) cell activity was assessed by 51 Cr-release assay, and the counts and percentages of CD4 + , CD8 + , and NK cells and their subsets in peripheral blood were measured before and after chemotherapy by two-color flow cytometry. Associations of cell population changes with chemotherapy responses were analyzed.
On univariate analysis, relative to grade (G) 1 effects, G 2 therapeutic effects were associated significantly with human epidermal growth factor receptor 2 (HER-2) + breast cancer (P = 0.024) and post-chemotherapy CD56 + CD16 - NK cell accumulation (8.4% vs. 5.5%, P = 0.042), and tended to be associated with increased pre-chemotherapy CD56 + CD16 - NK cell percentages (5.4% vs. 3.3%, P = 0.054) and pNK cell activity (42.0% vs. 34.5%, P = 0.057). The accumulation and increased percentage of CD56 + CD16 - NK cells in patients with G 2 effects were not associated with changes in pNK cell activity or the disappearance of axillary lymph-node metastases. On multivariate analysis, G 2 therapeutic effects tended to be associated with higher pre-chemotherapy pNK levels (odds ratio = 0.96; 95% confidence interval: 0.921 - 1.002; P = 0.067).
The accumulation of the immunoregulatory CD56 + CD16 - NK cell subset in the peripheral blood before and after chemotherapy may lead to the production of cytokines that induce an antitumor immune response. Activation of the immune response mediated by CD56 + CD16 - pNK cells after chemotherapy and their high counts before chemotherapy may contribute to the improvement of therapeutic effects against breast cancer.
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