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与 TIL(肿瘤浸润淋巴细胞)过继细胞治疗应答相关的外周免疫生物标志物

英文原题:Peripheral immune biomarkers associated with response to adoptive cell therapy with tumor infiltrating lymphocytes.

查看英文原题

Peripheral immune biomarkers associated with response to adoptive cell therapy with tumor infiltrating lymphocytes.

PubMed 2025/01/21(内容时间) Clin Exp Immunol Q2 · IF 3.9(JCR 2025)

研究概要

本研究调查了47例接受TIL-ACT的转移性黑色素瘤患者的外周血免疫景观,评估了治疗前后的抗肿瘤反应性和外周免疫细胞谱。

中文摘要

过继细胞治疗(ACT)使用体外扩增的TIL(肿瘤浸润淋巴细胞)(TILs,TIL-ACT)已在相当比例的转移性黑色素瘤患者中显示出临床疗效。为了进一步将TIL-ACT靶向应用于有应答的患者,识别预测性生物标志物并理解更广泛的免疫动态仍然至关重要。本研究调查了47例接受TIL-ACT的转移性黑色素瘤患者的外周血免疫景观,评估了治疗前后的抗肿瘤反应性和外周免疫细胞谱。应答者显示治疗后循环肿瘤反应性细胞频率增加,以及基线时活化的CD57表达T细胞水平较高,可作为应答的潜在生物标志物。相反,治疗后持续高血清水平的白细胞介素(IL)-6和IL-8、较高频率的CD38表达T细胞和调节性T细胞(Tregs)与不良结局相关。这些发现有助于理解与TIL-ACT应答相关的外周免疫景观,为预测性生物标志物和改善患者选择的机制提供了有价值的见解。

展开英文摘要原文

Adoptive cell therapy (ACT) with ex-vivo expanded tumor-infiltrating lymphocytes (TILs, TIL-ACT) has shown clinical efficacy in a significant proportion of patients with metastatic melanoma. To further target TIL-ACT toward responsive patients, identifying predictive biomarkers and understanding broader immune dynamics remain critical. This study investigated the peripheral blood immune landscape in 47 patients with metastatic melanoma undergoing TIL-ACT, assessing antitumor reactivity and peripheral immune cell profiles before and after treatment. Responders displayed increased frequency of circulating tumor-reactive cells post-treatment, and higher baseline levels of activated CD57-expressing T cells, serving as potential biomarkers of response. In contrast, persistent high serum levels of interleukin (IL)-6 and IL-8, higher frequencies of CD38-expressing T cells, and regulatory T cells (Tregs) post-treatment, correlated with unfavorable outcomes. These findings contribute to understanding the peripheral immune landscape associated with response to TIL-ACT, offering valuable insights into predictive biomarkers and mechanisms to improve patient selection.

论文信息

作者
Madsen CO、Velasco Santiago M、Martinenaite E、Holz Borch T、Donia M、Svane IM、Hansen M
单位
National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Herlev, Denmark.Denmark
期刊
Clinical and experimental immunology2025 Jan 21
原文标识
PubMed 39965099 · DOI 10.1093/cei/uxaf010