决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:CLEC10A can serve as a potential therapeutic target and its level correlates with immune infiltration in breast cancer.
CLEC10A可能是一个潜在生物标志物,可用于有效预测BC患者的预后。
乳腺癌(BC)是全球女性最常见的恶性肿瘤之一,严重威胁女性健康。C型凝集素结构域家族10成员A(CLEC10A)是C型凝集素受体家族的成员,此前已有报道称其可促进免疫细胞的抗肿瘤活性。在本研究中,利用癌症基因组图谱在线数据库的数据评估了CLEC10A表达在BC中的潜在预后价值。随后使用肿瘤免疫估计资源(TIMER)平台和阿拉巴马大学伯明翰分校癌症数据分析门户分析了BC与正常组织之间CLEC10A mRNA表达水平的差异。进行逆转录定量PCR以验证该分析的结果。使用Kaplan-Meier绘图数据库评估CLEC10A mRNA表达水平与BC临床预后之间的关联。基于CLEC10A mRNA表达水平与肿瘤免疫微环境之间的关联,利用TIMER平台和肿瘤与免疫系统相互作用数据库网站评估CLEC10A表达与肿瘤免疫细胞浸润程度之间的相关性。本研究发现,与正常组织相比,BC组织中CLEC10A表达显著降低,而这又与较差的临床结局相关。这表明较低的CLEC10A表达水平与BC的不良预后相关。此外,CLEC10A的表达水平被发现与BC中不同肿瘤浸润免疫细胞水平呈正相关,包括CD8 T细胞、B细胞、巨噬细胞和NK细胞,而这些又依次与一些基因标志物如CD19、CD8A、KIR2DS4和PTGS2密切相关。这些结果表明,BC中较低的CLEC10A表达水平与不良预后之间的关系可能是由于CLEC10A在肿瘤免疫微环境中的作用。总之,CLEC10A可能是一种潜在生物标志物,可用于有效预测BC患者的预后。
Breast cancer (BC) is one of the most common malignant cancers in females worldwide and greatly threatens women's health. The C-type lectin domain family 10 member A (CLEC10A) is a member of the C-type lectin receptor family that has been previously reported to promote the antitumor activity of immune cells. In the present study, the potential prognostic value of CLEC10A expression in BC was assessed using data from The Cancer Genome Atlas online database. Differences in the mRNA expression levels of CLEC10A between BC and normal tissues were then analyzed using the Tumor Immune Estimation Resource (TIMER) platform and the University of Alabama at Birmingham Cancer data analysis portal. Reverse transcription-quantitative PCR was performed to validate the results of this analysis. The Kaplan-Meier plotter database was used to evaluate the association between the mRNA expression levels of CLEC10A and clinical prognosis of BC. Based on the association between the mRNA expression levels of CLEC10A and the tumor immune microenvironment, the TIMER platform and the Tumor and Immune System Interaction Database website were utilized to assess the correlation between CLEC10A expression and the degree of tumor immune cell infiltration. The present study revealed that CLEC10A expression was significantly lower in BC tissues compared with that in normal tissues, which was in turn associated with poorer clinical outcomes. This suggested that lower CLEC10A expression levels were associated with unfavorable prognosis in BC. In addition, the expression level of CLEC10A was found to be positively associated with the level of different tumor-infiltrating immune cells in BC, including CD8 T cells, B cells, macrophages and NK cells which, was in turn closely correlated with some gene markers such as CD19, CD8A, KIR2DS4 and PTGS2. These results suggest that the relationship between lower CLEC10A expression level and poor prognosis in BC may be due to the role of CLEC10A in the tumor immune microenvironment. In conclusion, CLEC10A may be a potential biomarker that can be used to efficiently predict prognosis in patients with BC.
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