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:Thymosin α1 Combined with PD-1/PD-L1 Inhibitor Plus Chemotherapy in Platinum-Resistant Recurrent Ovarian Cancer : A Retrospective Analysis.
Thymosin α1 Combined with PD-1/PD-L1 Inhibitor Plus Chemotherapy in Platinum-Resistant Recurrent Ovarian Cancer : A Retrospective Analysis.
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在 PD-1/PD-L1 抑制剂为基础的化疗中加入 Tα1 可能增强铂耐药复发性卵巢癌患者的治疗效果、改善免疫应答并降低免疫抑制相关毒性。
铂耐药复发卵巢癌仍是一项重大治疗挑战。免疫检查点抑制剂(ICIs)联合化疗被广泛使用,但临床获益仍然有限。胸腺素α1(Tα1)是一种免疫调节肽,可能与ICIs产生协同作用以增强抗肿瘤免疫。
本回顾性研究纳入386例PROC患者,其中193例接受Tα1联合PD-1/PD-L1抑制剂及化疗(实验组),193例仅接受PD-1/PD-L1抑制剂及化疗(对照组)。比较两组的基线临床特征、临床疗效、免疫参数、无进展生存期(PFS)及不良事件。采用Kaplan-Meier生存分析和多因素Cox比例风险回归评估PFS及相关预后因素。连续变量和分类变量分别采用t检验和χ2检验进行比较。统计学显著性定义为p < 0.05。
两组基线特征具有可比性。实验组客观缓解率(43% vs 30.2%;p = 0.008)和疾病控制率(87% vs 69.8%;p = 0.000)显著更高。实验组中位 PFS 显著更长(3.0 vs 1.1 个月;HR = 3.22,95% CI:2.59-4.01;p = 0.000)。治疗后,实验组患者 IgA、IgG、IgM、CD3 +、CD4 +、CD4 + /CD8 + 比值和 NK 细胞水平较对照组显著升高(均 p < 0.01),而 CD8 水平保持相似。实验组不良事件发生率更低(50.8% vs 65.8%;χ 2 = 8.35,p = 0.004),主要由于骨髓抑制发生率降低。
Platinum-resistant recurrent ovarian cancer remains a major therapeutic challenge. Immune checkpoint inhibitors (ICIs) combined with chemotherapy are widely used, but clinical benefits remain limited. Thymosin α1 (Tα1), an immunomodulatory peptide, may synergize with ICIs to enhance anti-tumor immunity.
This retrospective study included 386 patients with PROC, with 193 patients receiving Tα1 combined with PD-1/PD-L1 inhibitors and chemotherapy (experimental group), and 193 patients receiving PD-1/PD-L1 inhibitors and chemotherapy alone (control group). Baseline clinical characteristics, clinical efficacy, immune parameters, progression-free survival (PFS), and adverse events were compared between the two groups. Kaplan-Meier survival analysis and multivariate Cox proportional hazards regression were used to assess PFS and associated prognostic factors. Continuous and categorical variables were compared using t -test and χ 2 -test, respectively. Statistical significance was defined as p < 0.05.
Baseline characteristics were comparable between the two groups. The experimental group showed significantly higher objective response rate (43% vs 30.2%; p = 0.008) and disease control rate (87% vs 69.8%; p = 0.000). The median PFS was significantly longer in the experimental group (3.0 vs 1.1 months; HR = 3.22, 95% CI: 2.59-4.01; p = 0.000). Post-treatment, patients in the experimental group demonstrated significantly elevated levels of IgA, IgG, IgM, CD3 + , CD4 + , CD4 + /CD8 + ratio, and NK cells compared to the control group (all p < 0.01), while CD8 levels remained similar. The incidence of adverse events was lower in the experimental group (50.8% vs 65.8%; χ 2 = 8.35, p = 0.004), primarily due to a reduced rate of myelosuppression.
The addition of Tα1 to PD-1/PD-L1 inhibitor-based chemotherapy may enhance treatment efficacy, improve immune response, and reduce immunosuppression-related toxicity in patients with platinum-resistant recurrent ovarian cancer.
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