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