研究概要
TIL(肿瘤浸润淋巴细胞)(TILs)是存在于肿瘤环境内的细胞,其中包括T细胞、B细胞和自然杀伤(NK)细胞。
中文摘要
TIL(肿瘤浸润淋巴细胞)(TILs)是存在于肿瘤环境中的细胞,其中包括T细胞、B细胞和自然杀伤(NK)细胞。目前,TILs已被用于多种癌症的免疫治疗。关于TILs在卵巢癌中过继转移的知识仍然有限,尤其是在TIL扩增方法方面。因此,我们研究的目的是比较两种卵巢癌TILs扩增方法之间T细胞克隆的质量。我们发现,经促有丝分裂刺激方法(低剂量IL-2联合抗人CD3/CD28)和标准刺激方法(仅高剂量IL-2)刺激的TILs均增加了T细胞总数。TCR repertoire分析显示,经标准刺激方法(仅高剂量IL-2)和促有丝分裂刺激方法(低剂量IL-2联合抗人CD3/CD28)刺激的TIL扩增T细胞之间,TCR repertoire模式不同。无论如何,当使用标准刺激方法(仅高剂量IL-2)扩增TILs时,CD4+和CD8+亚群TIL扩增克隆中使用的主要T细胞受体β可变(TRBV)链是相似的。此外,还存在仅在其中一个亚群中占优势的TIL扩增CD4+和CD8+ T细胞克隆。这些结果揭示了不同方案刺激后TIL质量的偏倚。需要进一步研究以理解TIL扩增的选择,从而实现更有效的过继转移治疗。
展开英文摘要原文
Tumor infiltrating lymphocytes (TILs) are cells that are present inside the tumor environment, of which include T cells, B cells and natural killer (NK) cells. At present, TILs are used for immunotherapy in various cancers. Knowledge on adoptive transfer of TILs in ovarian cancer is still limited, especially regarding TIL expansion methods. Therefore, the aim of our study was to compare the quality of T cell clones between two expansion methods for ovarian cancer TILs. We show that TILs stimulated with the mitogenic stimulation method (low dose IL-2 with anti-human CD3/CD28) and the standard stimulation method (high dose IL-2 only) both increased total number of T cells. TCR repertoire analyses revealed different TCR repertoire patterns between TIL-expanded T cells that were stimulated with the standard stimulation method (high dose IL-2 only) and the mitogenic stimulation method (low dose IL-2 with anti-human CD3/CD28). Regardless, when TILs were expanded using the standard stimulation method (high dose IL-2 only), the predominant T cell receptor beta variable (TRBV) chains that were used in both TIL-expanded clones of the CD4+ and CD8+ subpopulations were similar. In addition, there were also TIL-expanded CD4+ and CD8+ T cell clones that were dominant in only one or the other subpopulations. These results reveal the bias in TIL quality after being stimulated with different protocols. Further studies are required to understand the selection of TIL expansion, in order for a more efficacy adoptive transfer treatment.
论文信息
- 作者
- Kongkaew T、Thaiwong R、Tudsamran S、Sae-Jung T、Sengprasert P、Vasuratna A、Suppipat K、Reantragoon R
- 第一作者单位
- Immunology Division, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.Thailand
- 通讯作者单位
- Immunology Division, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Center of Excellence in Immunology and Immune-mediated Diseases, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. Electronic address: Rangsima.R@chula.ac.th.Thailand
- 文献类型
- 非美国政府资助研究
- 期刊
- Journal of immunological methods2022 Apr