晚期胆道癌患者LAG-3表达与化学免疫治疗疗效的关系

IF 4.6 2区 医学 Q2 IMMUNOLOGY Cancer Immunology, Immunotherapy Pub Date : 2025-01-03 DOI:10.1007/s00262-024-03878-0
Cheng-Yu Tang, Yi-Ting Lin, Yi-Chen Yeh, Shin-Yi Chung, Yu-Chan Chang, Yi-Ping Hung, San-Chi Chen, Ming-Huang Chen, Nai-Jung Chiang
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引用次数: 0

摘要

在我们之前针对晚期胆道癌(ABTC)的II期T1219试验中,纳武单抗与改性吉西他滨和S-1联合使用显示出有希望的疗效,而程序化死亡配体-1 (PD-L1)表达并不能预测化学免疫治疗的疗效。淋巴细胞活化基因-3 (LAG-3)是一种阴性免疫检查点,经常与PD-L1共表达。本研究评估了LAG-3表达在接受化疗免疫治疗的ABTC患者中的预测价值。我们对44例福尔马林固定的ABTC样本进行了PD-L1和LAG-3的免疫组化染色,并将其与化学免疫治疗的临床疗效进行了相关性分析。在选定的感兴趣的区域进行数字空间分析,以检查6例免疫细胞浸润和检查点表达。使用三个公共BTC数据集进行分析:TCGA-CHOL、GSE32225和GSE132305。38.6%的ABTC样本中LAG-3阳性,与PD-L1阳性显著相关(P < 0.001)。lag -3阳性肿瘤的客观缓解率(ORR)显著高于lag -3阴性肿瘤(70.6% vs. 33.3%, P = 0.029)。LAG-3表达水平与ORR升高相关(LAG-3 < 1%、1-9%和≥10%分别为33%、58%和100%);P = 0.018)和更高的治疗反应(分别为20.1%、38.6%和57.6%);P = 0.04)。LAG-3的表达与多个免疫检查点的表达呈正相关。在LAG-3阳性的BTC中观察到CD8+ T细胞的富集,这表明LAG-3的表达可能作为识别免疫炎症肿瘤和预测ABTC对化学免疫治疗反应的生物标志物。
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The correlation between LAG-3 expression and the efficacy of chemoimmunotherapy in advanced biliary tract cancer.

In our previous phase II T1219 trial for advanced biliary tract cancer (ABTC), the combination of nivolumab with modified gemcitabine and S-1 exhibited promising efficacy, while the programmed-death-ligand-1 (PD-L1) expression did not predict chemoimmunotherapy efficacy. Lymphocyte-activation-gene-3 (LAG-3), a negative immune checkpoint, is frequently co-expressed with PD-L1. This study assessed the predictive value of LAG-3 expression in ABTC patients who received chemoimmunotherapy. We analyzed 44 formalin-fixed ABTC samples using immunohistochemical staining for PD-L1 and LAG-3 and correlated them with the clinical efficacy of chemoimmunotherapy. Digital spatial profiling was conducted in selected regions of interest to examine immune cell infiltration and checkpoint expression in six cases. Three public BTC datasets were used for analysis: TCGA-CHOL, GSE32225, and GSE132305. LAG-3 positivity was observed in 38.6% of the ABTC samples and was significantly correlated with PD-L1 positivity (P < 0.001). The objective response rate (ORR) was significantly higher in LAG-3-positive tumors than in LAG-3-negative tumors (70.6% vs. 33.3%, P = 0.029). The LAG-3 expression level was associated with an increased ORR (33%, 58%, and 100% for LAG-3 < 1%, 1-9%, and ≥ 10%, respectively; P = 0.018) and a deeper therapeutic response (20.1%, 38.6%, and 57.6% for the same respective groups; P = 0.04). LAG-3 expression is positively correlated with the expression of numerous immune checkpoints. Enrichment of CD8+ T cells was observed in LAG-3-positive BTC, indicating that LAG-3 expression may serve as a biomarker for identifying immune-inflamed tumors and predicting the therapeutic response to chemoimmunotherapy in ABTC.

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来源期刊
CiteScore
10.50
自引率
1.70%
发文量
207
审稿时长
1 months
期刊介绍: Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
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