RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Characteristics of successful expansion of tumor-infiltrating lymphocytes from colorectal cancer liver metastasis.
Characteristics of successful expansion of tumor-infiltrating lymphocytes from colorectal cancer liver metastasis.
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利用TIL(肿瘤浸润淋巴细胞)(TILs)的过继细胞治疗(ACT)已成为多种恶性肿瘤的成功治疗模式。然而,从结直肠癌(CRC)肝转移灶中培养的TILs仍未被充分探索。15例CRC肝转移组织接受了TILs的初始扩增(IE)和快速扩增(REP)。由病理学家和深度学习衍生的空间分析评估了组织学检查,包括间质TILs水平和Klintrup-Mäkinen评分。
我们对扩增的TILs与组织病理学因素进行了相关性分析。所有病例均实现了成功的IE,每片段平均IE TIL计数和每例总IE TIL分别为2.59 ± 2.79e5个细胞和167.79 ± 126.97e5个细胞。5例进行了REP,中位倍数变化为3,610(范围,1,136-4,925)。IE TILs和REP TILs中CD4+/CD8+比率的中位数分别为3.66和0.68。每片段扩增TILs的平均数与KM评分之间观察到显著相关性(p = 0.022)。从CRC肝转移灶中成功扩增了TILs。KM评分的评估可能作为IE前可获得TILs的预测工具。这些发现为未来研究在转移性CRC患者中建立有效的ACT奠定了基础。
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-M kinen 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.
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