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
新辅助免疫治疗在局部晚期食管鳞状细胞癌中的疗效及淋巴细胞亚群预测因素：一项回顾性研究
英文原题：The efficacy of neoadjuvant immunotherapy and lymphocyte subset predictors in locally advanced esophageal squamous cell carcinoma: A retrospective study.
查看英文原题
The efficacy of neoadjuvant immunotherapy and lymphocyte subset predictors in locally advanced esophageal squamous cell carcinoma: A retrospective study.
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研究概要
PD-1 抑制剂联合化疗对局部晚期 ESCC 似乎具有前景。评估外周血免疫细胞的分化状态和动态变化可能为治疗疗效和预后提供有价值的预测见解。
研究思路结论见上方概要
背景
尽管PD-1/PD-L1抑制剂在晚期食管鳞状细胞癌（ESCC）中已显示出治疗潜力，但其在新辅助治疗中的作用及可靠的疗效生物标志物仍不明确。
方法
我们回顾性分析了2020年1月至2023年3月期间接受2周期铂类和紫杉醇为基础治疗后手术的局部晚期ESCC患者，治疗联合或不联合PD-1抑制剂。我们评估了外周血指标和三级淋巴结构（TLS）密度，以评价其对病理反应和预后的影响，从而构建用于预测疗效和生存的临床预测模型。
结果
在招募的157例患者中，106例接受免疫化疗（ICT），51例仅接受化疗（CT）。ICT组的病理缓解率（PRR）更优（47.2% vs. 29.4%，p = 0.034），不良事件和术后并发症相当。ICT组的中位无病生存期（DFS）为39.8个月，CT组未达到。ICT组的1年DFS率和总生存期（OS）率分别为73%和91%，CT组分别为68%和81%。我们发现较高的基线活化T细胞、较低的基线Treg细胞以及治疗后总淋巴细胞和CD4 + /CD8 + 比值下降预示PRR提高。治疗后CD4 + /CD8 + 比值降低和NK细胞增加与生存期延长相关，而TLS密度较高则提示预后较差。在ICT组中，治疗后CD4 + /CD8 + 比值较低提示DFS更长，治疗后B细胞减少提示OS更长。我们开发了一个整合这些预测因素的列线图，用于预测治疗效果和生存期。
展开英文摘要原文
BACKGROUND
Despite the recognized therapeutic potential of programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors in advanced esophageal squamous cell carcinoma (ESCC), their role in neoadjuvant therapy and reliable efficacy biomarkers remain elusive.
MATERIALS AND METHODS
We retrospectively analyzed locally advanced ESCC patients who underwent surgery following a 2-cycle platinum and paclitaxel-based treatment, with or without PD-1 inhibitors (January 2020-March 2023). We assessed peripheral blood indexes and tertiary lymphoid structures (TLS) density to evaluate their impact on pathological response and prognosis, leading to a clinical prediction model for treatment efficacy and survival.
RESULTS
Of the 157 patients recruited, 106 received immunochemotherapy (ICT) and 51 received chemotherapy (CT) alone. The ICT group demonstrated a superior pathological response rate (PRR) (47.2% vs. 29.4%, p = 0.034) with comparable adverse events and postoperative complications. The ICT group also showed a median disease-free survival (DFS) of 39.8 months, unattained by the CT group. The 1-year DFS and overall survival (OS) rates were 73% and 91% for the ICT group, and 68% and 81% for the CT group, respectively. We found higher baseline activated T cells, lower baseline Treg cells, and a decreased posttreatment total lymphocyte and CD4 + /CD8 + ratio predicted an enhanced PRR. Reduced posttreatment CD4 + /CD8 + ratio and increased NK cells were associated with prolonged survival, while higher TLS density indicated poorer prognosis. Among ICT group, a lower posttreatment CD4 + /CD8 + ratio indicated longer DFS and reduced posttreatment B cells indicated longer OS. A nomogram integrating these predictors was developed to forecast treatment efficacy and survival.
CONCLUSION
The combination of PD-1 inhibitors and chemotherapy appears promising for locally advanced ESCC. Evaluating the differentiation status and dynamic changes of peripheral blood immune cells may provide valuable predictive insights into treatment efficacy and prognosis.
论文信息
- 作者
- Wang R、Wen S、Du X、Xia J、Hu B、Zhang Y、Zhou G、Jiang F
- 单位
- Department of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Cancer medicine2024 Sep
- 原文标识
- PubMed 39275896 · DOI 10.1002/cam4.70228
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