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TIL(肿瘤浸润淋巴细胞)过继细胞治疗的耐药机制

英文原题:Mechanisms of resistance to adoptive cell therapy with tumor-infiltrating lymphocytes.

PubMed 2025/11/17(内容时间) Expert Rev Clin Immunol Q2 · IF 4(JCR 2025)

研究概要

TIL-ACT在特定用途之外显示出前景,但其成功取决于能否克服由患者、肿瘤和产品因素驱动的耐药性。要提高其疗效,需要精细的患者选择、TIL优化以及机制性见解,以指导新的、改进的治疗方法。

研究思路结论见上方概要

过继细胞治疗(ACT)联合TIL(肿瘤浸润淋巴细胞)已成为黑色素瘤患者的标准治疗,此前一项III期试验发表显示,与接受免疫检查点抑制剂ipilimumab治疗的患者相比,接受TIL-ACT治疗的转移性黑色素瘤患者的无进展生存期有所改善。近期临床试验也在其他免疫原性癌症患者中测试了TIL-ACT,包括非小细胞肺癌或宫颈癌。 涵盖领域:一些因素与TIL-ACT的长期缓解相关,包括输注给患者的细胞数量或CD8+与CD4+T细胞的比例。在此,我们总结了已知与TIL-ACT缓解或耐药相关的因素。我们还展望了哪些因素可以被改进,以克服耐药并提高患者的长期结局。

展开英文摘要原文

INTRODUCTION: Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) has become standard treatment for patients with melanoma after the publication of a phase III trial showing an improvement of progression-free survival of metastatic melanoma patients treated with TIL-ACT compared to patients treated with the immune checkpoint inhibitor ipilimumab. Recent clinical trials also tested TIL-ACT in patients with other immunogenic cancers including non-small cell lung cancer or cervical carcinomas. AREAS COVERED: Some factors were associated with long-term response to TIL-ACT including the number of cells applied to the patient or ratios of CD8 + versus CD4 + T cells. Here, we summarize known factors that are associated with response or resistance to TIL-ACT. We also give an outlook, which factors could be improved to overcome resistance and to enhance long-term outcome of patients. EXPERT OPINION: TIL-ACT shows promise beyond niche use, but its success depends on overcoming resistance driven by patient, tumor, and product factors. Advancing its efficacy will require refined patient selection, TIL optimization, and mechanistic insights to inform new, improved treatment approaches.

论文信息

作者
König D、Läubli H
单位
Division of Medical Oncology, University Hospital Basel, Basel, Switzerland.Switzerland
文献类型
综述 · 非美国政府资助研究
期刊
Expert review of clinical immunology2025 Dec
原文标识
PubMed 41213864 · DOI 10.1080/1744666X.2025.2588776