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肺腺癌免疫细胞浸润研究。

A Study on Immune Cell Infiltration in Lung Adenocarcinoma.

机构信息

Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.

出版信息

Comb Chem High Throughput Screen. 2022;25(12):2082-2088. doi: 10.2174/1386207325666220221100429.

Abstract

BACKGROUND

As a vital part of the tumor environment, immune cells affect the progression of tumors, and their composition and role vary in different types of tumors and influence prognosis. These immune cells have the potential to be beneficially targeted for immunotherapy, or, conversely, they may react negatively, even leading to drug resistance. For these reasons, probing into the composition and possible effects of immune cells in lung cancer is conducive to discovering valuable therapeutic targets.

MATERIALS AND METHODS

The lung adenocarcinoma gene expression data were downloaded from the TCGA database (https://cancergenome.nih.gov/; https://portal.gdc.cancer.gov/), and the lung adenocarcinoma gene expression matrix was converted into an immune cell-matrix using CIBERSORT software (https://cibersort.stanford.edu/), followed by an analysis of immune cells in lung adenocarcinoma tissues.

RESULTS

The results showed that among all immune cells in lung adenocarcinoma tissues, macrophages (Mφ) had the highest number, followed by T cells. The number of plasma cells in lung adenocarcinoma tissues was higher than in adjacent normal tissues. Compared with those in adjacent normal tissues, the number of resting memory clusters of differentiation 4 (CD4) T cells was lower, whereas active memory CD4 T cells were higher in lung adenocarcinoma tissues. In addition, the number of CD8 T cells was negatively related to that of resting memory CD4 T cells, with a correlation coefficient of -0.44, whereas it showed a positive association with the number of active memory CD4 T cells, with a correlation coefficient of 0.47. It was found that among various immune cells infiltrating lung adenocarcinoma tissues, unstimulated Mφ (M0), alternatively activated Mφ (M2), and resting memory CD4 T cells accounted for the largest proportions. However, these three types of immune cells were found to be lower in lung adenocarcinoma tissues than in adjacent normal tissues.

CONCLUSION

Immune cells infiltrating lung adenocarcinoma tissues are complex, which affect the development and progression of the tumor and may also be a significant cause of drug resistance. Studying the changes in immune cell infiltration during the development of specific types of tumors contributes to disease progression interpretation, prognosis assessment, and potential solutions to the existing drug resistance issue. In this paper, the status of immune cells in lung adenocarcinoma tissues was preliminarily discussed based on the database mining, but more experimental studies and in-depth discussions are needed in the future.

摘要

背景

免疫细胞作为肿瘤环境的重要组成部分,影响肿瘤的进展,其组成和作用在不同类型的肿瘤中有所不同,并影响预后。这些免疫细胞有可能成为免疫治疗的有益靶点,或者相反,它们可能会产生不良反应,甚至导致耐药性。出于这些原因,研究肺癌中免疫细胞的组成和可能的作用有助于发现有价值的治疗靶点。

材料和方法

从 TCGA 数据库(https://cancergenome.nih.gov/; https://portal.gdc.cancer.gov/)下载肺腺癌基因表达数据,并使用 CIBERSORT 软件(https://cibersort.stanford.edu/)将肺腺癌基因表达矩阵转换为免疫细胞矩阵,然后分析肺腺癌组织中的免疫细胞。

结果

结果表明,在肺腺癌组织中的所有免疫细胞中,巨噬细胞(Mφ)数量最多,其次是 T 细胞。肺腺癌组织中浆细胞的数量高于邻近正常组织。与邻近正常组织相比,肺腺癌组织中静息记忆 CD4 T 细胞的数量较低,而活跃记忆 CD4 T 细胞的数量较高。此外,CD8 T 细胞的数量与静息记忆 CD4 T 细胞的数量呈负相关,相关系数为-0.44,而与活跃记忆 CD4 T 细胞的数量呈正相关,相关系数为 0.47。研究发现,在浸润肺腺癌组织的各种免疫细胞中,未刺激的 Mφ(M0)、替代激活的 Mφ(M2)和静息记忆 CD4 T 细胞占比最大。然而,这三种类型的免疫细胞在肺腺癌组织中的含量低于邻近正常组织。

结论

浸润肺腺癌组织的免疫细胞复杂多样,影响肿瘤的发生和发展,也可能是导致耐药性的重要原因。研究特定类型肿瘤发展过程中免疫细胞浸润的变化有助于疾病进展解读、预后评估以及解决现有耐药问题。本文基于数据库挖掘初步探讨了肺腺癌组织中免疫细胞的状态,但未来还需要更多的实验研究和深入讨论。

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