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:Modulation of Peripheral Immune Cell Subpopulations After RapidArc/Moderate Hypofractionated Radiotherapy for Localized Prostate Cancer: Findings and Comparison With 3D Conformal/Conventional Fractionation Treatment.
Modulation of Peripheral Immune Cell Subpopulations After RapidArc/Moderate Hypofractionated Radiotherapy for Localized Prostate Cancer: Findings and Comparison With 3D Conformal/Conventional Fractionation Treatment.
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放疗(RT)是局限性前列腺癌(PC)患者的重要治疗选择。但放疗会导致外周淋巴细胞减少,从而影响患者免疫状态。本研究旨在观察两组采用不同技术及剂量分割方案接受根治性 RT 的 PC 患者,在 RT 后及 6 个月随访期间外周血免疫细胞亚群的变化,并调查免疫细胞调节与泌尿生殖或胃肠道毒性是否相关。共纳入 44 例接受根治性 RT 的局限性 PC 患者,治疗方案为 RapidArc/大分割或三维适形/常规分割。于基线、RT 结束时及 RT 后 3 和 6 个月分析白细胞总数、绝对淋巴细胞计数(ALC)和外周免疫细胞亚群。RT 结束时白细胞和 ALC 大幅下降;大分割组在 6 个月随访时呈恢复趋势,常规分割组则无此趋势。
此外,两组的 B 细胞、总 T 细胞、CD4⁺ T、CD8⁺ T 和 NK 细胞均显著下降;与另一技术/分割组相比,大分割组 B 细胞、总 T 细胞和 CD4⁺ T 淋巴细胞降幅较小。双阴性 T(DNT)、双阳性 T(DPT)和 NKT 细胞在 RT 结束时显著减少,随访期间略有恢复趋势,尤其在大分割组。未发现免疫细胞变化与泌尿生殖或胃肠道毒性相关。
本研究首次展示 RapidArc/中度大分割 RT 对局限性 PC 患者免疫细胞亚群的影响。鉴于人们日益关注少数 T 细胞亚群在免疫治疗中的作用,我们还纵向监测了 RT 对 DNT、DPT 和 NKT 的影响,此前尚无相关研究。初步数据强调,在 RT 与免疫疗法联合应用时代,应考虑不同 RT 技术/分割方案对外周免疫细胞的影响。
Radiotherapy (RT) is an important therapeutic option in patients with localized prostate cancer (PC). Unfortunately, radiation treatment causes a decrease in peripheral lymphocytes and, consequently, influences the patients' immune status.
Our aim was to study changes in peripheral blood immune cell subpopulations after RT and during 6 months' follow-up in 2 groups of PC patients irradiated with different techniques and dose fractions with curative intent.
We also investigated the presence of correlation between immune cell modulation and genitourinary or gastrointestinal toxicity.
We enrolled 44 patients treated with curative RT (RapidArc/hypofractionation regimen or 3D conformal/conventional fractionation) for localized PC. Total white blood cell (WBC), absolute lymphocyte counts (ALCs), and peripheral immune cell subpopulations were analyzed at baseline, at the end of RT, and 3 and 6 months after the end of RT. WBC and ALC greatly decreased at the end of RT with a trend to recover at 6 months' follow-up in the hypofractionation group but not in the conventional one.
Furthermore, B, total T, T CD4+, T CD8+, and NK cell values dropped significantly in both groups at the end of RT, with a minor decrease detectable in the hypofractionation group for B, total T, and T CD4+ lymphocytes with respect to the other technique/fractionation group. Double-negative T (DNT), double-positive T (DPT), and NKT cells significantly decreased at the end of RT with a slight tendency to recover values during follow-up, particularly in the hypofractionation group.
No correlation with genitourinary or gastrointestinal toxicity was found. In this study, we showed, for the first time, the effects of RapidArc/moderate hypofractionation RT on immune cell subsets in patients treated for localized PC. Due to the growing interest in minority T-cell subpopulations for immunotherapy, we also reported longitudinal monitoring of the effects of RT on DNT, DPT, and NKT, which was never studied before.
Our preliminary data highlight the importance of considering the effects of different RT techniques/fractionation regimens on peripheral immune cells, in the era of RT and immunotherapy combination.
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