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:The potential applications of peptide-loading complex in cancer treatment.
The potential applications of peptide-loading complex in cancer treatment.
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近年来癌症免疫治疗取得重大进展,尤其使血液系统疾病患者的预后显著改善。然而,将这些成果推广至实体瘤仍面临困难。肽负载复合物(PLC)是内质网(ER)中短暂形成的多亚基膜复合体,对启动层级化免疫应答至关重要。PLC 由分子伴侣钙网蛋白和 tapasin、仅见于 I 类糖蛋白的硫氧还蛋白 ERp57,以及抗原加工相关转运体组成。PLC 协调主要组织相容性复合体 I 类(MHC-I)分子的肽装载和编辑,并将肽转运至 ER。迄今发现的肿瘤免疫逃逸策略之一是改变 MHC 分子的表达,因为 MHC 抗原对于向 T 淋巴细胞呈递抗原以及调节 NK 细胞活性都至关重要。
此外,MHC-I 表达降低与对基于 T 细胞的癌症免疫疗法耐药有关,此类疗法包括过继转移抗肿瘤 CD8 T 细胞或免疫检查点抑制。PLC 能结合多种 MHC-I 等位基因变体,因此在 T 细胞启动、分化和控制肿瘤生长方面不可或缺。本综述探讨 PLC 在各类癌症中的功能和影响,以促进癌症治疗策略改进。
Immunotherapy for cancer has made significant strides in the last several years. The prognosis for cancer patients has significantly improved as a result, particularly in hematological diseases.
However, it was discovered that translating these achievements to solid tumors proved challenging. The peptide-loading complex (PLC), a temporary multisubunit membrane assembly in the endoplasmic reticulum (ER), is crucial for initiating a hierarchical immune response. Chaperones calreticulin and tapasin make up the PLC, unique to class I glycoproteins, thiooxido-reductase ERp57, and a transporter associated with antigen processing.
The loading and editing of major histocompatibility complex class I (MHC-I) molecules with peptide translocation into the ER are synchronized by the PLC. One of the immune escape strategies revealed for tumors so far is changes in the expression of MHC molecules. This is because MHC antigens are crucial in presenting antigens to T-lymphocytes and controlling NK cell activity.
Furthermore, decreased MHC-I expression has been linked to malignancies resistant to T-cell-based cancer immunotherapies (adoptive transfer of antitumor CD8 T-cells or checkpoint inhibition). The PLC is essential for T-cell priming, differentiation, and tumor growth control because it can bind to a wide range of MHC-I allomorphs. In this review, we have looked into PLC's function and effects in all forms of cancer to improve cancer therapy techniques.
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