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:Delineation of colorectal cancer ligand-receptor interactions and their roles in the tumor microenvironment and prognosis.
Delineation of colorectal cancer ligand-receptor interactions and their roles in the tumor microenvironment and prognosis.
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通过对现有配体-受体对进行全面深入的探究,本研究为 CRC 亚型分类提供了新思路,为 CRC 患者提供了新的风险筛查工具,并为 CRC 治疗提供了潜在的配体-受体对靶点和通路。
靶向配体-受体相互作用(LRIs)的免疫疗法在结直肠癌(CRC)治疗中进展迅速,且LRIs也影响CRC发展的诸多方面。然而,CRC中LRIs的模式及其对肿瘤微环境和临床价值的影响仍不明确。
我们描绘了来自29例CRC患者的55,539个单细胞RNA测序(scRNA-seq)样本以及包含1411例CRC患者数据的三个bulk RNA-seq数据集中LRIs的模式。随后,全面研究了肿瘤微环境、免疫治疗和CRC患者预后的影响。
我们计算了25种细胞类型之间1893个配体-受体对的强度,以重建CRC的空间结构。我们基于LRIs识别了肿瘤亚型,揭示了亚型与免疫治疗疗效之间的关系,并探索了影响TIL(肿瘤浸润淋巴细胞)丰度的配体-受体对和特异性靶点。最后,构建并验证了基于配体-受体对的预后模型。
Immunotherapies targeting ligand-receptor interactions (LRIs) are advancing rapidly in the treatment of colorectal cancer (CRC), and LRIs also affect many aspects of CRC development. However, the pattern of LRIs in CRC and their effect on tumor microenvironment and clinical value are still unclear.
We delineated the pattern of LRIs in 55,539 single-cell RNA sequencing (scRNA-seq) samples from 29 patients with CRC and three bulk RNA-seq datasets containing data from 1411 CRC patients. Then the influence of tumor microenvironment, immunotherapy and prognosis of CRC patients were comprehensively investigated.
We calculated the strength of 1893 ligand-receptor pairs between 25 cell types to reconstruct the spatial structure of CRC. We identified tumor subtypes based on LRIs, revealed the relationship between the subtypes and immunotherapy efficacy and explored the ligand-receptor pairs and specific targets affecting the abundance of tumor-infiltrating lymphocytes. Finally, a prognostic model based on ligand-receptor pairs was constructed and validated.
Overall, through the comprehensive and in-depth investigation of the existing ligand-receptor pairs, this study provides new ideas for CRC subtype classification, a new risk screening tool for CRC patients, and potential ligand-receptor pair targets and pathways for CRC therapy.
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