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
T 细胞因子 1（TCF-1）决定结直肠癌中的 T 细胞分化
英文原题：T cell factor 1 (TCF-1) defines T cell differentiation in colorectal cancer.
查看英文原题
T cell factor 1 (TCF-1) defines T cell differentiation in colorectal cancer.
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中文摘要
前体耗竭型（T pex）CD8+ T细胞的存在对于在免疫检查点抑制（ICI）治疗后维持强健免疫至关重要。在II-III期错配修复（MMR）缺陷型（dMMR）结直肠癌（CRC）患者中，对ICI的显著应答正在显现。
我们发现64%的dMMR和15%的错配修复正常型（pMMR）III期CRC具有高频率的TIL（肿瘤浸润淋巴细胞）（TIL-hi）。
此外，CD8+ T细胞表达TCF-1（Tcf7）预测患者预后改善，且T pex细胞（CD3+CD8+TCF-1+PD-1+）在III期CRC的淋巴聚集区内大量存在。相比之下，CD3+CD8+TCF-1-PD-1+细胞在浸润前沿和肿瘤核心更为丰富，而T细胞在所有肿瘤区域中的丰度相当。有趣的是，在TIL-hi dMMR和TIL-hi pMMR CRC之间未观察到T pex细胞频率的差异。
因此，TIL-hi CRC中T pex细胞功能及ICI缓解率值得进一步研究。
展开英文摘要原文
The presence of precursor to exhausted (T pex ) CD8 + T cells is important to maintain robust immunity following treatment with immune checkpoint inhibition (ICI). Impressive responses to ICI are emerging in patients with stage II-III mismatch repair (MMR)-deficient (dMMR) colorectal cancer (CRC).
We found 64% of dMMR and 15% of mismatch repair-proficient (pMMR) stage III CRCs had a high frequency of tumor infiltrating lymphocytes (TIL-hi).
Furthermore, expression of TCF-1 (Tcf7) by CD8 + T cells predicted improved patient prognosis and T pex cells (CD3 + CD8 + TCF-1 + PD-1 + ) were abundant within lymphoid aggregates of stage III CRCs. In contrast, CD3 + CD8 + TCF-1 - PD-1 + cells were more abundant at the invasive front and tumor core, while T cells were equally abundant in all tumor areas. Interestingly, no differences in the frequency of T pex cells were observed between TIL-hi dMMR and TIL-hi pMMR CRCs.
Therefore, T pex cell function and ICI response rates in TIL-hi CRC warrants further investigation.
论文信息
- 作者
- Tran K、Kumari AN、Raghu D、Cox DRA、Goh SK、Perini MV、Muralidharan V、Tebbutt NC
- 单位
- Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia.Germany
- 期刊
- iScience2024 Sep 20
- 原文标识
- PubMed 39280606 · DOI 10.1016/j.isci.2024.110754
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