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过继性 T 细胞免疫疗法对不可切除或复发性胆管癌患者免疫细胞谱和预后的影响。

Effects of adoptive T-cell immunotherapy on immune cell profiles and prognosis of patients with unresectable or recurrent cholangiocarcinoma.

机构信息

Department of Gastroenterology, Public Central Hospital of Matto Ishikawa, Hakusan, Japan.

Innovative Clinical Research Center, Kanazawa University, Kanazawa, Japan.

出版信息

Int J Cancer. 2024 Feb 15;154(4):738-747. doi: 10.1002/ijc.34716. Epub 2023 Sep 7.

DOI:10.1002/ijc.34716
PMID:37676069
Abstract

The identification of immune cell profiles (ICP) involved in anti-tumor immunity is crucial for immunotherapy. Therefore, we herein investigated cholangiocarcinoma patients (CCA) who received adoptive T-cell immunotherapy (ATI). Eighteen unresectable or recurrent CCA received ATI of αβ T cells alone or combined with chemotherapy. ICP were evaluated by flow cytometry. There were 14 patients with intrahepatic cholangiocarcinoma (iCCA) and four with distal cholangiocarcinoma (dCCA). After one course of treatment, nine iCCA and four dCCA had progressive disease (PD), while five iCCA had stable disease (SD). Median overall survival (OS) was prolonged to 21.9 months. No significant differences were observed in OS between the PD and SD groups of iCCA. The frequency of helper T cells (HT) in iCCA decreased from 70.3% to 65.5% (P = .008), while that of killer T cells (KT) increased from 27.0% to 30.6% (P = .005). dCCA showed no significant changes of immune cells. OS was prolonged in iCCA with increased frequencies of CD3+ T cells (CD3) (P = .039) and αβ T cells (αβ) (P = .039). dCCA showed no immune cells associated with OS. The frequencies of CD3+ T cells and αβ T cells in the PD group for iCCA decreased from 63.5% to 53% (P = .038) and from 61.6% to 52.2% (P = .028), respectively. In the SD group, the frequency of HT decreased from 65.8% to 56.9% (P = .043), whereas that of KT increased from 30.1% to 38.3% (P = .043). In conclusions, ATI affected ICP and prolonged OS. Immune cells involved in treatment effects differed according to the site of cholangiocarcinoma.

摘要

鉴定参与抗肿瘤免疫的免疫细胞表型(ICP)对于免疫疗法至关重要。因此,我们在此研究了接受过过继性 T 细胞免疫疗法(ATI)的胆管癌患者(CCA)。18 例不可切除或复发的 CCA 单独或联合化疗接受了 αβ T 细胞的 ICP。通过流式细胞术评估 ICP。其中 14 例为肝内胆管癌(iCCA),4 例为远端胆管癌(dCCA)。在一个疗程的治疗后,9 例 iCCA 和 4 例 dCCA 疾病进展(PD),而 5 例 iCCA 病情稳定(SD)。中位总生存期(OS)延长至 21.9 个月。iCCA 的 PD 和 SD 组之间的 OS 无显著差异。iCCA 中的辅助性 T 细胞(HT)频率从 70.3%降至 65.5%(P=0.008),而杀伤性 T 细胞(KT)从 27.0%增至 30.6%(P=0.005)。dCCA 的免疫细胞无显著变化。iCCA 中 CD3+T 细胞(CD3)(P=0.039)和 αβ T 细胞(αβ)(P=0.039)频率增加,OS 延长。dCCA 中没有与 OS 相关的免疫细胞。iCCA 的 PD 组中 CD3+T 细胞和 αβ T 细胞的频率从 63.5%降至 53%(P=0.038)和从 61.6%降至 52.2%(P=0.028),而 SD 组中的 HT 频率从 65.8%降至 56.9%(P=0.043),而 KT 频率从 30.1%增至 38.3%(P=0.043)。总之,ATI 影响 ICP 并延长 OS。参与治疗效果的免疫细胞根据胆管癌的部位而有所不同。

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