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

IF 3.4 3区医学 Q3 IMMUNOLOGY

Clinical and experimental immunology Pub Date : 2025-01-21 DOI:10.1093/cei/uxaf010

Cecilie Oelvang Madsen, Marta Velasco Santiago, Evelina Martinenaite, Troels Holz Borch, Marco Donia, Inge Marie Svane, Morten Hansen

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引用次数: 0

Abstract

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.

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与肿瘤浸润淋巴细胞过继细胞治疗反应相关的外周免疫生物标志物。

体外扩增肿瘤浸润淋巴细胞（TILs, TIL-ACT）的过继细胞疗法（ACT）在很大比例的转移性黑色素瘤患者中显示出临床疗效。为了进一步针对反应性患者靶向TIL-ACT，确定预测性生物标志物和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景观，评估了治疗前后的抗肿瘤反应性和外周血免疫细胞谱。应答者在治疗后循环肿瘤反应细胞的频率增加，激活表达cd57的T细胞的基线水平更高，这是应答的潜在生物标志物。相反，治疗后持续高水平的血清白细胞介素(IL)-6和IL-8，表达cd38的T细胞和调节性T细胞（Tregs）的频率较高，与不利的结果相关。这些发现有助于理解与TIL-ACT反应相关的外周免疫景观，为预测性生物标志物和机制提供有价值的见解，以改善患者选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical and experimental immunology 医学-免疫学

CiteScore

8.40

自引率

2.20%

发文量

101

审稿时长

3-8 weeks

期刊介绍： Clinical & Experimental Immunology (established in 1966) is an authoritative international journal publishing high-quality research studies in translational and clinical immunology that have the potential to transform our understanding of the immunopathology of human disease and/or change clinical practice. The journal is focused on translational and clinical immunology and is among the foremost journals in this field, attracting high-quality papers from across the world. Translation is viewed as a process of applying ideas, insights and discoveries generated through scientific studies to the treatment, prevention or diagnosis of human disease. Clinical immunology has evolved as a field to encompass the application of state-of-the-art technologies such as next-generation sequencing, metagenomics and high-dimensional phenotyping to understand mechanisms that govern the outcomes of clinical trials.