免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:TIMM13 as a prognostic biomarker and associated with immune infiltration in skin cutaneous melanoma (SKCM).
TIMM13 as a prognostic biomarker and associated with immune infiltration in skin cutaneous melanoma (SKCM).
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TIMM13 可能是 SKCM 的预后生物标志物。它可能调节肿瘤免疫微环境并导致更差预后。此外,有必要研究 TIMM13 的靶向治疗。
该蛋白作为分子伴侣样蛋白,防止聚集并引导疏水性前体穿过线粒体膜间隙。SLC25A12通过与TIMM13相互作用而被TIMM8导入。尽管如此,TIMM13与皮肤黑色素瘤(SKCM)及TIL(肿瘤浸润淋巴细胞)(TILs)的相互作用仍不清楚。
TIMM13在SKCM中的异常表达及其临床结局通过多个数据库进行评估,包括仙桃工具(https://www.xiantao.love/)、HPA和UALCAN。应用TISIDB和肿瘤免疫估计资源(TIMER)数据库探讨TIMM13与肿瘤浸润免疫细胞的关联。构建OS列线图,并检验模型性能。最后,通过免疫组织化学(IHC)验证TIMM13蛋白表达。
TIMM13 在 SKCM 样本中的表达高于瘤周样本。TIMM13 与样本类型、亚组、癌症分期、淋巴结分期和更差的生存期密切相关。此外,TIMM13 的上调与免疫调节因子、趋化因子以及 T 细胞、B 细胞、单核细胞、中性粒细胞、巨噬细胞和 T 细胞调节因子显著相关。生物信息学数据分析发现,TIMM13 表达与 PD1(T 细胞耗竭标志物)密切相关。基于校准图的列线图显示出良好的预测性能。TIMM13 在黑色素瘤组织样本中的表达高于正常样本。
Providing protection against aggregation and guiding hydrophobic precursors through the mitochondria's intermembrane space, this protein functions as a chaperone-like protein. SLC25A12 is imported by TIMM8 as a result of its interaction with TIMM13. In spite of this, it is still unknown how TIMM13 interacts with skin cutaneous melanoma (SKCM) and tumor-infiltrating lymphocytes (TILs).
Aberrant expression of TIMM13 in SKCM and its clinical outcome was evaluated with the help of multiple databases, including the Xiantao tool (https://www.xiantao.love/), HPA, and UALCAN. TISIDB and Tumor Immune Estimation Resources (TIMER) databases were applied to explore the association between TIMM13 and tumor infiltration immune cells. OS nomogram was constructed, and model performance was examined. Finally, TIMM13 protein expression was validated by immunohistochemistry (IHC).
TIMM13 expression was higher in SKCM samples than in peritumor samples. TIMM13 was strongly associated with sample type, subgroup, cancer stage, lymph node stage, and worse survival. Further, upregulation of TIMM13 was significantly associated with immunoregulators, and chemokines, as well as T cells, B cells, monocytes, neutrophils, macrophages, and T-cell regulators. An analysis of bioinformatic data uncovered that TIMM13 expression was strongly associated with PD1 (T-cell exhaustion marker). The nomogram showed good predictive performance based on calibration plot. TIMM13 was highly expressed in melanoma tissue samples than in normal samples.
In brief, TIMM13 may be a prognostic biomarker for SKCM. It might modulate the tumor immune microenvironment and lead to a poorer prognosis. In addition, it is necessary to study the targeted therapy of TIMM13.
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