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
结直肠癌中终末耗竭 CD8(+) T 细胞的免疫基因组特征与预后意义
英文原题：Immunogenomic characteristics and prognostic implications of terminally exhausted CD8(+) T cells in colorectal cancers.
查看英文原题
Immunogenomic characteristics and prognostic implications of terminally exhausted CD8(+) T cells in colorectal cancers.
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研究概要
Ttex 浸润与 MSI 和 TMB 状态相关，可能作为结直肠癌的预后标志物。
研究思路结论见上方概要
背景
T细胞耗竭是免疫逃逸的主要机制。近年来，祖细胞耗竭T细胞（Tpex）和终末耗竭T细胞（Ttex）在多种癌症类型中的治疗和预后意义已被探索。本研究探讨了结直肠癌（CRCs）中Tpex和Ttex的免疫基因组学特征及其预后意义。
方法
我们采用多重免疫荧光（mIF）技术，使用针对CK、CD3、CD8、TCF1和FOXP3的抗体，评估了517例III期或高危II期结直肠癌（CRC）患者中TIL（肿瘤浸润淋巴细胞）（TILs）的多种亚群。我们将这些TIL亚群的浸润水平与CRC的遗传特征进行了比较，包括微卫星不稳定性（MSI）、肿瘤突变负荷（TMB）以及五个生物学通路中40个肿瘤相关基因的突变。
结果
CD8 + T细胞密度、CD8/CD3比值及Ttex/CD8 + T细胞比值在微卫星不稳定高和肿瘤突变负荷高的肿瘤中升高。生存分析显示，较高的CD8 + T细胞密度、较高的调节性T细胞/CD3 + T细胞比值及较高的Ttex/CD8 + T细胞比值与更好的5年无复发生存（RFS）率相关。当肿瘤被分为CD8高、CD8低/Ttex低和CD8低/Ttex高三组时，CD8高组和CD8低/Ttex高组的5年RFS优于CD8低/Ttex低组。
展开英文摘要原文
METHODS
We performed multiplex immunofluorescence (mIF) using antibodies against CK, CD3, CD8, TCF1, and FOXP3 to assess diverse subsets of tumor-infiltrating lymphocytes (TILs) in 517 patients with stage III or high-risk stage II CRCs. We compared the infiltration level of these TIL subsets with the genetic profiles of CRCs, including microsatellite instability (MSI), tumor mutational burden (TMB), and mutations in 40 tumor-associated genes across five biological pathways.
RESULTS
CD8 + T cell density, the CD8/CD3 ratio, and the Ttex/CD8 + T cell ratio were elevated in microsatellite instability-high and tumor mutational burden-high tumors. Survival analysis showed that, higher CD8 + T cell density, higher regulatory T cell/CD3 + T cell ratio, and higher Ttex/CD8 + T cell ratio exhibited better 5-year relapse-free survival (RFS) rates. When tumors were categorized into CD8-high, CD8-low/Ttex-low, and CD8-low/Ttex-high groups, the CD8-high and CD8-low/Ttex-high groups showed better 5-year RFS than the CD8-low/Ttex-low group. DISCUSSION: Ttex infiltration is associated with MSI and TMB status and may serve as a prognostic marker of CRCs.
论文信息
- 作者
- Lee JA、Park HE、Lee DW、Han SW、Kim TY、Jeong SY、Park KJ、Bae JM
- 第一作者单位
- Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-Do, Republic of Korea.South Korea
- 通讯作者单位
- Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.South Korea
- 期刊
- Frontiers in immunology2025
- 原文标识
- PubMed 40519933 · DOI 10.3389/fimmu.2025.1601188
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