Mechanisms of resistance to adoptive cell therapy with tumor-infiltrating lymphocytes.

IF 4 3区医学 Q2 IMMUNOLOGY

Expert Review of Clinical Immunology Pub Date : 2025-12-01 Epub Date: 2025-11-17 DOI:10.1080/1744666X.2025.2588776

David König, Heinz Läubli

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引用次数: 0

Abstract

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.

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肿瘤浸润淋巴细胞对过继细胞治疗的耐药性机制。

在一项III期试验发表后，采用肿瘤浸润淋巴细胞（TIL）的过继细胞疗法（ACT）已成为黑色素瘤患者的标准治疗方法，该试验显示，与使用免疫检查点抑制剂ipilimumab治疗的患者相比，使用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。最近的临床试验还测试了TIL-ACT在其他免疫原性癌症（包括非小细胞肺癌或宫颈癌）患者中的应用。涵盖的领域：一些因素与TIL-ACT的长期疗效相关，包括应用于患者的细胞数量或CD8+与CD4+ T细胞的比例。在这里，我们总结了与TIL-ACT反应或耐药相关的已知因素。我们也给出了一个前景，哪些因素可以改善，以克服耐药性和提高患者的长期结果。专家意见：TIL-ACT的前景超出了利基用途，但其成功取决于克服由患者、肿瘤和产品因素驱动的耐药性。提高其疗效将需要精确的患者选择，TIL优化和机制见解，以告知新的，改进的治疗方法。

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

Expert Review of Clinical Immunology IMMUNOLOGY-

CiteScore

7.60

自引率

2.30%

发文量

221

审稿时长

6-12 weeks

期刊介绍： Expert Review of Clinical Immunology (ISSN 1744-666X) provides expert analysis and commentary regarding the performance of new therapeutic and diagnostic modalities in clinical immunology. Members of the International Editorial Advisory Panel of Expert Review of Clinical Immunology are the forefront of their area of expertise. This panel works with our dedicated editorial team to identify the most important and topical review themes and the corresponding expert(s) most appropriate to provide commentary and analysis. All articles are subject to rigorous peer-review, and the finished reviews provide an essential contribution to decision-making in clinical immunology. Articles focus on the following key areas: • Therapeutic overviews of specific immunologic disorders highlighting optimal therapy and prospects for new medicines • Performance and benefits of newly approved therapeutic agents • New diagnostic approaches • Screening and patient stratification • Pharmacoeconomic studies • New therapeutic indications for existing therapies • Adverse effects, occurrence and reduction • Prospects for medicines in late-stage trials approaching regulatory approval • Novel treatment strategies • Epidemiological studies • Commentary and comparison of treatment guidelines Topics include infection and immunity, inflammation, host defense mechanisms, congenital and acquired immunodeficiencies, anaphylaxis and allergy, systemic immune diseases, organ-specific inflammatory diseases, transplantation immunology, endocrinology and diabetes, cancer immunology, neuroimmunology and hematological diseases.