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:CD103-Positive Tumor-Infiltrating Lymphocytes Predict a Favorable Prognosis in Colorectal Cancer with Liver Metastasis.
CD103-Positive Tumor-Infiltrating Lymphocytes Predict a Favorable Prognosis in Colorectal Cancer with Liver Metastasis.
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这些发现揭示了 CD103 + TILs 在 PT 和 LM 组织内空间分布的异质性。值得注意的是,LM 中 CD103 + TILs 的浸润可作为 CRLM 患者的预后生物标志物。
CD103+ TIL 高浸润与结直肠癌患者生存改善相关。然而,CD103+ TIL 在结直肠癌肝转移(CRLM)中的空间分布及临床意义仍不清楚。
本研究纳入84例接受原发结直肠肿瘤(PT)和肝转移灶(LM)同期手术切除的CRLM患者。采用免疫组化评估不同瘤内区域CD103 + TILs的丰度。此外,进行多重免疫荧光分析以评估CD103 + TIL亚群。利用已发表的数据集,进行单细胞RNA测序(scRNA-seq)和空间转录组分析,以研究PT和LM之间CD103 + CD8 + T细胞的功能差异。
PT中CD103 + TILs的存在与CRLM患者的预后无关。相反,LM中CD103 + TILs浸润增加与生存结局改善相关。值得注意的是,LM肿瘤中心间质区域中的CD103 + TILs成为CRLM患者的独立预后因素。CRLM组织中的大多数CD103 + TILs被鉴定为CD8 + CD103 + 细胞,其次是CD4 + CD103 + 细胞。scRNA-seq分析显示,PT中的CD103 + CD8 + T细胞表现出CD8 + 细胞毒性T细胞的典型特征,而LM中的这些细胞则表现出组织驻留记忆T细胞的特征。
High infiltration of CD103 + tumor infiltrating lymphocytes (TILs) is associated with improved patient survival in colorectal cancer. However, the spatial distribution and clinical significance of CD103 + TILs in colorectal liver metastasis (CRLM) remain unclear.
This study enrolled 84 patients with CRLM who underwent simultaneous surgical resection of both primary colorectal tumors (PT) and liver metastases (LM). The abundance of CD103 + TILs in different intratumoral compartments were evaluated using immunohistochemistry. Additionally, multiplex immunofluorescence analysis was performed to assess CD103 + TIL subsets. Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomic analysis were performed to investigate the functional differences of CD103 + CD8 + T cells between PT and LM using a published dataset.
The presence of CD103 + TILs in PT did not correlate with the prognosis of patients with CRLM. Conversely, an increased infiltration of CD103 + TILs in LM was associated with improved survival outcomes. Notably, CD103 + TILs in the stromal compartments of the tumor center of LM emerged as an independent prognostic factor for CRLM patients. The majority of CD103 + TILs in CRLM tissues were identified as CD8 + CD103 + cells, followed by CD4 + CD103 + cells. scRNA-seq analysis showed that the CD103 + CD8 + T cells in the PT exhibit characteristics typical of CD8 + cytotoxic T cells, while those in the LM display features of tissue-resident memory T cells.
These findings reveal the heterogeneity in the spatial distribution of CD103 + TILs within both PT and LM tissues. Notably, the infiltration of CD103 + TILs in LM serves as a prognostic biomarker for CRLM patients.
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