Nguyen Linh T, Lo Charlotte S, Fyrsta Michael, Nie Jessica, Yam Jennifer Y, Yen Pei-Hua, Le Michael X, Hersey Karen, Kenk Miran, Crumbaker Megan, Fleshner Neil, Kulkarni Girish, Hamilton Robert, Jewett Michael, Finelli Antonio, Evans Andrew, Sweet Joan, Ohashi Pamela S, Joshua Anthony M
Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
Kinghorn Cancer Centre, St Vincent's Hospital, Garvan Institute of Medical Research, Sydney, Australia.
Prostate Cancer. 2022 Jun 16;2022:6499344. doi: 10.1155/2022/6499344. eCollection 2022.
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.
This study examined the expansion of TILs from prostate adenocarcinoma, as a preliminary step to evaluate the potential of TILs for adoptive T cell therapy. . Malignant and adjacent nonmalignant tissues were obtained from fifteen men undergoing radical prostatectomy. . There were no study interventions. . Expanded cells were analysed by flow cytometry, and the data was assessed for associations between cell subpopulations and expansion rate.
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 CD3CD56 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.
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.
实体恶性肿瘤中肿瘤浸润淋巴细胞(TILs)的评估为肿瘤微环境中的免疫调节提供了见解,也推动了过继性T细胞疗法的发展和优化。
本研究检测前列腺腺癌中TILs的扩增情况,作为评估TILs用于过继性T细胞疗法潜力的初步步骤。从15例接受根治性前列腺切除术的男性患者中获取恶性及相邻非恶性组织。本研究未进行干预措施。通过流式细胞术分析扩增的细胞,并评估细胞亚群与扩增率之间的相关性。
15个恶性标本中有9个(60%)的肿瘤浸润淋巴细胞能够扩增至产生治疗性输注产品所需的数量。CD4 T细胞多于CD8 T细胞(CD4中位数为56.8%,CD8为30.0%),此外,TILs扩增更快与CD4 T细胞比例更高相关(生长较快的培养物中中位数为69.8%;生长较慢的培养物中为36.8%)。在恶性标本培养物中,CD3CD56细胞与CD3细胞的比例更高与TILs扩增较慢相关(生长较慢的培养物中中位数为13.3%,生长较快的培养物中为2.05%),但在非恶性标本培养物中无此现象。
扩增TILs用于潜在治疗用途是可行的。我们的研究结果还表明,进一步研究前列腺腺癌中的TILs可能有助于深入了解肿瘤微环境中T细胞的调节机制。需要进一步研究来评估它们的治疗潜力。