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:Characteristics and developmental trajectory of clinical trials focused on tumor-infiltrating lymphocytes for cancer treatment.
TIL(肿瘤浸润淋巴细胞)在癌症免疫治疗中显示出前景,但其临床应用和发展轨迹仍缺乏充分表征。
TIL(肿瘤浸润淋巴细胞)在癌症免疫治疗中展现出前景,但其临床应用和发展轨迹尚未得到充分描述。本研究对截至2024年12月31日在ClinicalTrials.gov注册、评估TIL癌症治疗的介入性临床试验进行了横断面描述性分析,系统评估试验特征、时间趋势和治疗策略。纳入的177项试验绝大多数处于早期阶段,受试者规模较小;最常研究的肿瘤类型为恶性黑色素瘤。北美开展的试验总数最多,近年来试验活动和行业资助快速增长,亚洲尤为明显。最常见的联合策略为细胞因子支持和免疫检查点抑制剂(ICI)。自2017年以来,研究者对TIL单药治疗及TIL联合ICI的兴趣日益增加。与选择性扩增TIL的试验相比,基因工程化TIL试验较少采用细胞因子支持或非清髓性化疗;而选择性扩增TIL试验则更常评估放疗作为联合策略。总体而言,TIL治疗临床试验主要仍处于早期探索阶段。细胞因子和ICI仍是主要的联合治疗方法,而TIL单药治疗逐渐成为增长趋势。仍需持续开展研究和临床试验,以支持TIL疗法在癌症治疗中得到更广泛、更加标准化的应用。
Tumor-infiltrating lymphocytes (TIL) have shown promise in cancer immunotherapy, yet their clinical application and developmental trajectory remain insufficiently characterized. In this study, we conducted a cross-sectional, descriptive analysis of interventional clinical trials investigating TIL therapies for cancer treatment registered on ClinicalTrials.gov up to December 31, 2024. Trial characteristics, temporal trends, and treatment strategies were systematically assessed. Among 177 eligible trials, the vast majority were early-phase studies enrolling small patient cohorts. Malignant melanoma was the most frequently studied tumor type. North America conducted the largest number of trials overall, while recent years have seen rapid growth in trial activity and industry sponsorship, particularly in Asia. Cytokine support and immune checkpoint inhibitors (ICIs) were the most common combination strategies. Since 2017, increasing interest has been observed in TIL monotherapy and in TIL-ICI combinations. Genetically engineered TIL trials were less likely to incorporate cytokine support or non-myeloablative chemotherapy, whereas selectively expanded TIL trials more frequently evaluated radiotherapy as a combination strategy. Overall, clinical trials of TIL therapy have primarily focused on early-phase exploration. Cytokines and ICIs remain the predominant combination approaches, while the use of TIL monotherapy has emerged as a growing trend. Continued research efforts and clinical investigation are essential to support the broader and more standardized application of TIL-based therapies in cancer treatment.
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