Madsen Cecilie Oelvang, Velasco Santiago Marta, Martinenaite Evelina, Holz Borch Troels, Donia Marco, Svane Inge Marie, Hansen Morten
National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Herlev, Denmark.
Clin Exp Immunol. 2025 Jan 21;219(1). doi: 10.1093/cei/uxaf010.
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.
采用体外扩增的肿瘤浸润淋巴细胞进行过继性细胞治疗（ACT，即TIL-ACT）已在相当一部分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靶向于有反应的患者，识别预测性生物标志物并了解更广泛的免疫动力学仍然至关重要。本研究调查了47例接受TIL-ACT治疗的转移性黑色素瘤患者的外周血免疫格局，评估了治疗前后的抗肿瘤反应性和外周免疫细胞谱。有反应者在治疗后循环肿瘤反应性细胞的频率增加，且活化的表达CD57的T细胞基线水平较高，可作为反应的潜在生物标志物。相比之下，治疗后白细胞介素（IL）-6和IL-8的血清水平持续升高、表达CD38的T细胞频率较高以及调节性T细胞（Tregs）与不良预后相关。这些发现有助于理解与TIL-ACT反应相关的外周免疫格局，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。
