为肝细胞癌武装 GPC3 CAR-T 细胞:多少才足够,下一步是什么?
Armouring GPC3 CAR T cells for hepatocellular carcinoma: how much is enough and what comes next?
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Identification of LOXL3-associating immune infiltration landscape and prognostic value in hepatocellular carcinoma.
Identification of LOXL3-associating immune infiltration landscape and prognostic value in hepatocellular carcinoma.
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近年来,免疫检查点抑制剂(ICIs)在肿瘤免疫治疗领域的突破带来了治疗革命,已被证明可改善肝细胞癌(HCC)患者的预后。免疫浸润是肿瘤微环境(TME)的主要组成部分,在肿瘤进展和治疗反应中均发挥重要作用。肿瘤免疫治疗中尚未解决的主要挑战是探索TME促进HCC管理的内在和外在机制。赖氨酰氧化酶样3(LOXL3)参与细胞外基质(ECM)的重塑以及胶原和弹性纤维的交联。已有报道表明LOXL3与多种类型癌症的发生发展和肿瘤形成相关。从癌症基因组图谱(TCGA)数据库中提取RNA测序数据及相应的临床信息,然后利用R包进行基因表达、肿瘤微环境、生存和富集分析。
在本研究中,我们首次发现LOXL3基因在肿瘤组织中较正常组织上调。此外,LOXL3表达与HCC中多种免疫细胞的浸润及免疫检查点基因的表达呈正相关。
同时,高LOXL3表达预示HCC患者预后不良。功能富集分析提示LOXL3主要与细胞外结构和基质组织、细胞间黏附以及T细胞活化相关。这是首个全面研究表明LOXL3与免疫浸润相关,并可能作为预测HCC预后和免疫治疗的新型生物标志物。
In recent years, breakthroughs in the field of tumor immunotherapy with immune checkpoint inhibitors (ICIs) have made a therapeutic revolution, which has been shown to improve the prognosis of patients with hepatocellular carcinoma (HCC). Immune infiltrates represent a major component of tumor microenvironment (TME), and play an essential role in both tumor progression and therapeutic response. The major unmet challenge in tumor immunotherapy is exploring the intrinsic and extrinsic mechanisms of TME promoting the management of HCC.
Lysyl oxidase like 3 (LOXL3) participates in the remodeling of extracellular matrix (ECM) and the cross-linking of collagen and elastic fibers. It has been reported that LOXL3 is associated with the development and tumorigenesis of multiple types of cancer.
RNA sequencing data and corresponding clinical information were extracted from The Cancer Genome Atlas (TCGA) databases, then subjected to gene expression, tumor microenvironment, survival, enrichment analyses utilizing R packages. In this study, we first found that LOXL3 gene was upregulated in tumor tissues compared with the normal tissues.
Furthermore, LOXL3 expression is positively correlated with the infiltration of multiple immune cells and the expression of immune checkpoint genes in HCC. Meanwhile, high LOXL3 expression predicted poor outcomes of the patients with HCC.
Functional enrichment analysis suggested that LOXL3 was mainly linked to extracellular structure and matrix organization, cell-cell adhesion, and T cell activation. This is the first comprehensive study to indicate that LOXL3 is correlated with immune infiltrates and may serve as a novel biomarker predicting prognosis and immunotherapy in HCC.
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