单细胞追踪揭示黑色素瘤 TIL 治疗过程中肿瘤反应性 T 细胞的可塑性
Single-cell tracking reveals tumor-reactive T cell plasticity during melanoma TIL therapy.
TIL(肿瘤浸润淋巴细胞)过继细胞治疗可在转移性黑色素瘤中诱导持久缓解,然而在体外扩增过程中及回输后,调控肿瘤反应性T细胞命运的克隆和转录动态仍知之甚少。
英文原题:Adoptive cell therapy for cancer: combination strategies and biomarkers.
过继性细胞疗法 (ACT) 是一种治疗方法,包括在体外分离、改造和扩增免疫细胞,然后将其回输到患者体内以增强抗肿瘤免疫应答。
过继细胞治疗(ACT)是一种治疗方法,包括在体外分离、改造并扩增免疫细胞,然后重新输注至患者体内,以增强抗肿瘤免疫应答。多种 ACT 已在多种癌症中显示出有希望的临床结局。例如,CAR-T、TIL(肿瘤浸润淋巴细胞)疗法及 TCR 工程化 T 细胞(TCR-T)疗法均已获得美国 FDA 批准。然而,ACT 的临床应用仍受到疗效有限及可能危及生命的毒性所限制。疗效下降可能源于免疫抑制性肿瘤微环境、细胞迁移和浸润不足、输注细胞耗竭、肿瘤异质性以及抗原逃逸。为应对这些挑战,研究者开发了旨在增强疗效并管理不良反应的联合策略,其中纳入了传统治疗及非 ACT 类免疫疗法。生物标志物对优化 ACT 策略并应对相关复杂问题至关重要,可用于候选患者选择、评估 ACT 产品质量、监测长期疗效、管理毒性及指导联合方案。本综述简要介绍 6 种 ACT 模式及其常见局限,总结现有联合策略,探讨潜在未来方案,并概述与 ACT 相关的生物标志物。这些见解可为开发和临床实施更有效的 ACT 疗法提供指导,最终改善患者结局。
Adoptive cell therapy (ACT) is a therapeutic approach that involves the isolation, modification, and expansion of immune cells ex vivo , followed by their reinfusion into the patient to enhance anti-tumor immune responses. Various forms of ACT have demonstrated promising clinical outcomes across multiple types of cancer. For example, chimeric antigen receptor (CAR)-T cell therapy, tumor-infiltrating lymphocyte (TIL) therapy, and T-cell receptor-engineered T cell (TCR-T) therapy have received approval from the US Food and Drug Administration. However, the clinical application of ACT remains constrained by limited efficacy and potentially life-threatening toxicities. Diminished efficacy may result from an immunosuppressive tumor microenvironment, poor trafficking and infiltration, exhaustion of infused cells, tumor heterogeneity, and antigen escape. To address these challenges, combination strategies have been developed with the goals of enhancing efficacy and managing adverse effects. Conventional treatments and non-ACT forms of immunotherapy have been incorporated into these combination approaches. Biomarkers play an essential role in optimizing ACT strategies and addressing associated complexities. They can aid in candidate selection, assess the quality of ACT products, monitor long-term therapeutic efficacy, manage toxicity, and guide combination regimens. This review briefly outlines six ACT modalities and their common limitations, summarizes current combination strategies, explores potential future regimens, and offers an overview of biomarkers relevant to ACT. These insights provide valuable guidance for the development and clinical implementation of more effective ACT-based therapies, ultimately aiming to improve patient outcomes.
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