肿瘤细胞治疗研究
英文原题：Phenotypic alterations in immune cells and their association with toxicities in postoperative endometrial cancer patients undergoing brachytherapy.
近距离放疗通过上调NK/NKT细胞增强固有免疫激活，这可能与急性直肠炎的发生相关。这些发现突出表明，免疫调节可作为管理放疗诱导毒性的前瞻性生物标志物。
本研究旨在探讨接受近距离放射治疗的中危子宫内膜癌术后患者外周血免疫细胞，特别是NK细胞、NKT细胞、总B细胞、总T细胞及其亚群的表型变化，并探讨其与不良反应的关联。
本研究纳入了一组92例患者，他们于2022年1月至2024年11月在山西省肿瘤医院接受了近距离放射治疗（每次5.0 Gy，共6次）。采用流式细胞术在治疗前、治疗期间和治疗后对免疫细胞亚群进行定量，包括CD45 + CD3 - CD16 + CD56 + NK细胞、CD3 + CD56 + NKT细胞、CD45 + CD3 - CD19 + B细胞、CD3 + CD8 + T细胞、CD3 + CD4 + CD4 + 辅助T细胞、CD3 + CD8 + 细胞毒性T细胞、CD45 + CD4 - CD25 HI CD127 LO 调节性T细胞。应用多种统计方法分析这些表型变化，并采用卡方检验探讨其与毒性的关联。
与治疗前水平相比，NK细胞和NKT细胞在治疗期间及治疗后显著升高（P<0.001，P=0.003），而B细胞显著降低（P<0.001）。在整个治疗过程中，总T细胞及其亚群计数未见明显变化（P>0.05）。近距离放疗引起的副作用轻微，未观察到II级或以上毒性。NK细胞水平升高组的急性放射性直肠炎发生率显著高于未升高组（31.9% vs. 8.7%，P=0.028）。其他各组之间放射性直肠炎、膀胱炎和阴道炎的发生率无显著差异（P>0.05）。
OBJECTIVE: This study aims to investigate the phenotypic alterations in peripheral blood immune cells, especially natural killer (NK) cells, natural killer T (NKT) cells, total B cells, total T cells and their subsets, in postoperative patients with intermediate-risk endometrial cancer undergoing brachytherapy, and explores their association with adverse reactions. METHODS: A cohort of ninety-two patients, who received brachytherapy (5.0 Gy per fraction, 6 fractions) at Shanxi Cancer Hospital from January 2022 to November 2024, was included in this study. Immune cell subsets, including CD45 + CD3 - CD16 + CD56 + NK cells, CD3 + CD56 + NKT cells, CD45 + CD3 - CD19 + B cells, CD3 + CD8 + T cells, CD3 + CD4 + CD4 + helper T cells, CD3 + CD8 + Cytotoxic T cells, CD45 + CD4 - CD25 HI CD127 LO Regulatory T cells, were quantified using flow cytometry pre-, during, and post- treatment. Various statistical methods were applied to analyze these phenotypic changes and the chi-square test was employed to explore their association with toxicities. RESULTS: Compared to pre-treatment levels, NK cells and NKT cells increased significantly during and post-treatment (P<0.001, P=0.003), while B cells decreased significantly(P<0.001). No notable alterations were observed in the counts of total T cells and their subsets throughout the treatment process (P>0.05). Brachytherapy caused mild side effects, with no toxicities of grade II or higher observed. The incidence of acute radiation proctitis was significantly higher in the group with elevated NK cell levels compared to the non-elevated group (31.9% vs. 8.7%, P=0.028). The incidence of radiation proctitis, cystitis, and vaginitis did not differ significantly among the other groups (P>0.05). CONCLUSION: Brachytherapy enhances innate immune activation through the upregulation of NK/NKT cells, potentially correlating with the development of acute proctitis. These findings highlight immune modulation as a prospective biomarker for managing radiotherapy-induced toxicity.
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