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组织驻留记忆 T 细胞浸润增加预示肝外胆管癌对抗 PD-L1 免疫治疗的良好反应

英文原题:Increased Infiltration of Tissue-Resident Memory T Cells Predicts a Good Response to Anti-PD-L1 Immunotherapy in Extrahepatic Cholangiocarcinoma.

PubMed 2025/07/25(内容时间) Pathobiology Q3 · IF 1.7(JCR 2025)

研究概要

肿瘤内CD8+和CD103+ T细胞可能作为eCCA中ICI疗效的预测生物标志物,突显组织驻留免疫细胞作为治疗靶点。

研究思路结论见上方概要

肝外胆管癌(eCCA)是一种侵袭性强、预后差的恶性肿瘤。靶向PD-L1的免疫检查点抑制剂(ICIs)可增强抗肿瘤免疫,但可靠的预测性生物标志物仍不明确。本研究探讨了肿瘤浸润免疫细胞,包括T细胞和巨噬细胞,作为eCCA中ICI疗效潜在生物标志物的价值。

对15例术后复发或不可切除的eCCA患者接受durvalumab治疗进行了回顾性分析。采用免疫组化染色评估切除肿瘤标本中PD-L1、HLA-I/II类、CD8和CD103的表达。采用RECIST 1.1标准评估ICI反应,分为部分缓解(PR)、疾病稳定(SD)或疾病进展(PD)。分析免疫细胞浸润与临床结局之间的相关性。

5例患者达到PR,5例SD,5例PD。PR和SD组肿瘤巢内CD8+和CD103+ T细胞浸润显著高于PD组(p = 0.032,p = 0.0147)。HLA-I类高表达与缓解相关,而PD-L1和HLA-II类未见显著关联。CD8+CD103+ T细胞增多的患者表现出更好的疾病控制。

展开英文摘要原文

INTRODUCTION: Extrahepatic cholangiocarcinoma (eCCA) is an aggressive malignancy with a poor prognosis. Immune checkpoint inhibitors (ICIs) targeting PD-L1 enhance antitumor immunity, but reliable predictive biomarkers remain unclear. This study investigated tumor-infiltrating immune cells, including T cells and macrophages, as potential biomarkers for ICI efficacy in eCCA. METHODS: A retrospective analysis was conducted on 15 eCCA patients who received durvalumab for recurrent or unresectable disease after surgery. Immunohistochemical staining assessed PD-L1, HLA-class I/II, CD8, and CD103 expression in resected tumor specimens. ICI response was evaluated using RECIST 1.1 criteria and classified as partial response (PR), stable disease (SD), or progressive disease (PD). Correlations between immune cell infiltration and clinical outcomes were analyzed. RESULTS: Five patients achieved PR, five SD, and five PD. CD8+ and CD103+ T-cell infiltration within tumor nests was significantly higher in PR and SD groups than in PD (p = 0.032, p = 0.0147). High HLA-class I expression correlated with response, while PD-L1 and HLA-class II showed no significant association. Patients with increased CD8+CD103+ T cells demonstrated better disease control. CONCLUSION: Intratumoral CD8+ and CD103+ T cells may serve as predictive biomarkers for ICI efficacy in eCCA, highlighting tissue-resident immune cells as therapeutic targets.

论文信息

作者
Tagayasu Y、Yamada R、Kanemitsu K、Kondo Y、Fujiwara Y、Tanizaki T、Itoyama R、Kitano Y
第一作者单位
Department of Cell Pathology, Graduate School of Medicine, Kumamoto University, Kumamoto, Japan.Japan
通讯作者单位
Department of Gastroenterological Surgery, Graduate School of Medicine, Kumamoto University, Kumamoto, Japan, maiwa217@kumamoto-u.ac.jp.Japan
期刊
Pathobiology : journal of immunopathology, molecular and cellular biology2026
原文标识
PubMed 40716424 · DOI 10.1159/000547222