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从成人肉瘤中分离与扩增 TIL(肿瘤浸润淋巴细胞)的潜力探索

英文原题:Investigating the Potential of Isolating and Expanding Tumour-Infiltrating Lymphocytes from Adult Sarcoma.

PubMed 2022/01/21(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

研究概要

我们的结果表明,某些肉瘤亚型有潜力产生足够数量的TIL用于TIL治疗。

中文摘要

肉瘤是一组异质性间充质肿瘤,其中许多与高转移风险和不良预后相关。传统化疗和靶向治疗在不同个体和肿瘤亚型中的效果各异。目前的治疗往往临床获益有限;因此,迫切需要更有效的治疗方法。免疫治疗的最新进展,如检查点抑制或过继细胞治疗(ACT),显示出通过提供更个性化的治疗来提高疗效的潜力。TIL(肿瘤浸润淋巴细胞)(TILs)治疗是免疫治疗中的一个新兴领域。在此,我们收集了190例未接受术前辅助治疗患者的肉瘤肿瘤标本,以分离TILs。我们比较了不同的TIL扩增方法,并优化了一套专门针对肉瘤TIL培养效果的方案。扩增后的TIL群体通过流式细胞术分析使用CD3、CD4、CD8、CD14、CD19和CD56标记进行表征。TIL群体经非特异性刺激以建立TIL反应性。通过优化的扩增方案,从92例原发性肉瘤标本中的54例成功分离并培养了TILs。分离的TILs在CD4+和CD8+T细胞组成上存在差异,并保留了刺激后释放IFN的能力。我们的结果表明,某些肉瘤亚型有潜力产生足够数量的TILs用于TIL治疗。

展开英文摘要原文

Sarcomas are a heterogeneous group of mesenchymal neoplasms, many of which are associated with a high risk of metastasis and poor prognosis. Conventional chemotherapy and targeted therapies have varying effects across individuals and tumour subtypes. The current therapies frequently provide limited clinical benefit; hence, more effective treatments are urgently needed. Recent advances in immunotherapy, such as checkpoint inhibition or adoptive cell therapy (ACT), show potential in increasing efficacy by providing a more personalized treatment. Therapy with tumour-infiltrating lymphocytes (TILs) is an emerging field in immunotherapy. Here, we collected 190 sarcoma tumour specimens from patients without pre-operative adjuvant treatment in order to isolate TILs. We compared different methods of TIL expansion and optimized a protocol specifically for efficacy in culturing TILs from sarcoma. The expanded TIL populations were characterized by flow cytometry analysis using CD3, CD4, CD8, CD14, CD19 and CD56 markers. The TIL populations were non-specifically stimulated to establish TIL reactivity. Through an optimized expansion protocol, TILs were isolated and cultured from 54 of 92 primary sarcoma specimens. The isolated TILs varied in CD4 + and CD8 + T-cell compositions and retained their ability to release IFN upon stimulation. Our results suggest that certain sarcoma subtypes have the potential to yield a sufficient number of TILs for TIL therapy.

论文信息

作者
Ko A、Coward VS、Gokgoz N、Dickson BC、Tsoi K、Wunder JS、Andrulis IL
单位
Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.Canada
期刊
Cancers2022 Jan 21
原文标识
PubMed 35158816 · DOI 10.3390/cancers14030548