Baek Jina, Choi Gyuheon, Lee GunHee, Lee Hyun, Gong Gyungyub, Park Hye Seon, Lim Chae-Lyul, Kim Joo Young, Lee Hee Jin
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.
Department of Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Sci Rep. 2025 Jan 10;15(1):1639. doi: 10.1038/s41598-025-85892-5.
Adoptive cell therapy (ACT) utilizing tumor-infiltrating lymphocytes (TILs) has emerged as a successful treatment modality for various malignancies. However, TILs cultured from colorectal cancer (CRC) liver metastasis remain underexplored. Fifteen CRC liver metastasis tissues underwent initial expansion (IE) of TILs and rapid expansion (REP). Histologic examination including the level of stromal TILs and Klintrup-Mäkinen score, were assessed by pathologists and deep learning-derived spatial analysis. We performed correlation analysis between expanded TILs and histopathologic factors. All cases exhibited successful IE, with a mean IE TIL count per fragment and total IE TIL per case of 2.59 ± 2.79e5 cells and 167.79 ± 126.97e5 cells, respectively. Five cases underwent REP, with a median fold change of 3,610 (range, 1,136-4,925). The median CD4+/CD8 + ratio in IE TILs and REP TILs were 3.66 and 0.68, respectively. A significant correlation was observed between the mean number of expanded TILs per fragment and KM score (p = 0.022). Successful expansion of TILs from CRC liver metastasis was achieved. Assessment of KM score may serve as a predictive tool for the obtainable TILs before IE. These findings lay the groundwork for future studies to establish effective ACT in patients with metastatic CRC.
利用肿瘤浸润淋巴细胞（TILs）的过继性细胞疗法（ACT）已成为治疗各种恶性肿瘤的一种成功治疗方式。然而，从结直肠癌（CRC）肝转移灶培养的TILs仍未得到充分研究。对15个CRC肝转移组织进行了TILs的初始扩增（IE）和快速扩增（REP）。病理学家和深度学习衍生的空间分析评估了包括基质TILs水平和Klintrup-Mäkinen评分在内的组织学检查。我们对扩增的TILs与组织病理学因素进行了相关性分析。所有病例均成功进行了IE，每个片段的平均IE TIL计数和每个病例的总IE TIL分别为2.59±2.79×10⁵个细胞和167.79±126.97×10⁵个细胞。5例进行了REP，中位倍增变化为3610（范围1136 - 4925）。IE TILs和REP TILs中的中位CD4⁺/CD8⁺比值分别为3.66和0.68。观察到每个片段扩增的TILs平均数与KM评分之间存在显著相关性（p = 0.022）。成功实现了从CRC肝转移灶扩增TILs。KM评分的评估可作为IE前可获得的TILs的预测工具。这些发现为未来在转移性CRC患者中建立有效的ACT研究奠定了基础。
