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TP53 状态对肿瘤微环境中 CD8+ T 细胞浸润作用的生物信息学分析。

A bioinformatic analysis of the role of TP53 status on the infiltration of CD8+ T cells into the tumor microenvironment.

机构信息

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.

Department of General Pathology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt.

出版信息

Braz J Med Biol Res. 2023 Oct 20;56:e12970. doi: 10.1590/1414-431X2023e12970. eCollection 2023.

Abstract

CD8+ T cells play basic roles in the immune system in a tumor microenvironment (TME) to fight cancer. Several reports have suggested signs of the involvement of tumor protein p53 (TP53) in a complex immune system network. Moreover, our previous research indicated that TP53 orchestrates the polarization and infiltration of macrophages into the TME. In the present study, the clinical function of TP53 status (wild/mutant) in CD8+ T cell infiltration was assessed using more than 10,000 The Cancer Genome Atlas (TCGA) samples from 30 cancer types through Tumor Immune Estimation (TIMER). Our investigation revealed that CD8+ T cell infiltration was higher in head and neck squamous cell carcinoma (HNSC) and uterine corpus endometrial carcinoma (UCEC) patients with wild-type TP53 than in those with mutant TP53. Wild-type TP53 conferred a good prognosis for HNSC and UCEC (P<0.05). In contrast, CD8+ T cell infiltration in lung adenocarcinoma (LUAD) patients with wild-type TP53 was much lower than in those with mutant TP53. Notably, clinical outcomes for LUAD with wild-type TP53 were poor (P<0.05). This study was the first to provide insights into the novel association of TP53 with CD8+ T cells infiltration in the TME in patients with HNSC, LUAD, and UCEC. Therefore, TP53 status acts as a prognostic marker, and this can be used as a basis to further study the effect of targeting TP53 in these patients. Furthermore, our study found that TP53 status was a reliable predictive factor and therapeutic target in patients with HNSC and UCEC.

摘要

CD8+ T 细胞在肿瘤微环境 (TME) 中在免疫系统中发挥基本作用,以对抗癌症。有几项报告表明,肿瘤蛋白 p53 (TP53) 的迹象参与了复杂的免疫系统网络。此外,我们之前的研究表明,TP53 协调巨噬细胞向 TME 的极化和浸润。在本研究中,通过肿瘤免疫估计 (TIMER) 使用来自 30 种癌症类型的超过 10000 个癌症基因组图谱 (TCGA) 样本评估了 TP53 状态(野生型/突变型)在 CD8+ T 细胞浸润中的临床功能。我们的研究表明,与突变型 TP53 相比,野生型 TP53 的头颈部鳞状细胞癌 (HNSC) 和子宫体子宫内膜癌 (UCEC) 患者的 CD8+ T 细胞浸润更高。野生型 TP53 为 HNSC 和 UCEC 提供了良好的预后 (P<0.05)。相比之下,野生型 TP53 的肺腺癌 (LUAD) 患者的 CD8+ T 细胞浸润远低于突变型 TP53。值得注意的是,LUAD 患者的野生型 TP53 的临床结局较差 (P<0.05)。这项研究首次提供了有关 TP53 与 HNSC、LUAD 和 UCEC 患者 TME 中 CD8+ T 细胞浸润的新关联的见解。因此,TP53 状态作为一种预后标志物,这可以作为进一步研究在这些患者中靶向 TP53 效果的基础。此外,我们的研究发现,TP53 状态是 HNSC 和 UCEC 患者的可靠预测因子和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac65/10591486/2d82d9fd63d9/1414-431X-bjmbr-56-e12970-gf001.jpg

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