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:Expansion of Lymphocytes from Prostatic Adenocarcinoma and Adjacent Nonmalignant Tissue.
Expansion of Lymphocytes from Prostatic Adenocarcinoma and Adjacent Nonmalignant Tissue.
将 TILs 扩增用于潜在治疗用途是可行的。
背景:实体瘤中TIL(肿瘤浸润淋巴细胞)的研究揭示了肿瘤微环境中的免疫调节机制,并推动了过继T细胞疗法的发展和优化。目的:本研究评估前列腺腺癌中TIL的体外扩增,作为初步探索TIL过继细胞治疗潜力的步骤。设计、场所和参与者:从15名接受根治性前列腺切除术的男性患者中取得恶性组织及邻近非恶性组织。研究未实施干预。结局测量与统计分析:采用流式细胞术分析扩增细胞,并评估细胞亚群与扩增速度的关联。结果:15份恶性标本中有9份(60%)可将TIL扩增至足以制备治疗性输注产品的数量。CD4+ T细胞占优势,高于CD8+ T细胞(CD4+中位56.8%,CD8+中位30.0%);扩增较快的培养物中CD4+ T细胞比例较高(中位69.8%,慢速扩增培养物为36.8%)。在恶性组织培养物中,CD3−CD56+细胞相较CD3+细胞比例较高与TIL扩增较慢有关(慢速培养中位13.3%,快速培养为2.05%);非恶性组织培养物未见此关联。结论:扩增TIL以供潜在治疗用途是可行的。研究结果也提示,进一步研究前列腺腺癌TIL可能有助于了解肿瘤微环境中T细胞调节机制,仍需进一步评估其治疗潜力。
BACKGROUND: The evaluation of tumour-infiltrating lymphocytes (TILs) in solid malignancies has yielded insights into immune regulation within the tumour microenvironment and has also led to the development and optimisation of adoptive T cell therapies. OBJECTIVES: This study examined the in vitro expansion of TILs from prostate adenocarcinoma, as a preliminary step to evaluate the potential of TILs for adoptive T cell therapy. Design, Setting, and Participants . Malignant and adjacent nonmalignant tissues were obtained from fifteen men undergoing radical prostatectomy. Interventions . There were no study interventions. Outcome Measurements and Statistical Analysis . Expanded cells were analysed by flow cytometry, and the data was assessed for associations between cell subpopulations and expansion rate. RESULTS: Tumour-infiltrating lymphocytes could be expanded to numbers that would be needed to generate a therapeutic infusion product from nine of 15 malignant specimens (60%). The CD4 + T cells predominated over CD8 + T cells (median 56.8% CD4 + , 30.0% CD8 + ), and furthermore, faster TIL expansion was associated with a higher proportion of CD4 + T cells (median 69.8% in faster-growing cultures; 36.8% in slower-growing cultures). A higher proportion of CD3 - CD56 + cells versus CD3 + cells was associated with slower TIL expansion in cultures from malignant specimens (median 13.3% in slower-growing cultures versus 2.05% in faster-growing cultures), but not from nonmalignant specimens. CONCLUSIONS: The expansion of TILs for potential therapeutic use is feasible. Our findings also indicate that further examination of TILs from prostate adenocarcinomas may yield insights into mechanisms of regulation of T cells within the tumour microenvironment. Further research is required to evaluate their therapeutic potential.
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