The prognostic effect of infiltrating immune cells is shaped by proximal M2 macrophages in lung adenocarcinoma

IF 27.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Cancer Pub Date : 2024-09-04 DOI:10.1186/s12943-024-02080-1
Jian-Rong Li, Vikram Shaw, Yupei Lin, Xiang Wang, Muhammad Aminu, Yong Li, Jia Wu, Jianjun Zhang, Christopher I. Amos, Chao Cheng
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Abstract

The spatial arrangement of immune cells within the tumor microenvironment (TME) and their interactions play critical roles in the initiation and development of cancer. Several advanced technologies such as imaging mass cytometry (IMC) providing the immunological landscape of the TME with single-cell resolution. In this study, we develop a new method to quantify the spatial proximity between different cell types based on single-cell spatial data. Using this method on IMC data from 416 lung adenocarcinoma patients, we show that the proximity between different cell types is more correlated with patient prognosis compared to the traditional features such immune cell density and fractions. Consistent with previous reports, our results validate that proximity of T helper (Th) and B cells to cancer cells is associated with survival benefits. More importantly, we discover that the proximity of M2 macrophages to multiple immune cells is associated with poor prognosis. When Th/B cells are stratified into M2-distal and M2-proximal, the abundance of the former but not the latter category of Th/B cells is correlated with enhanced patient survival. Additionally, the abundance of M2-distal and M2-proximal cytotoxic T cells (Tc) is respectively associated with good and poor prognosis. Our results indicate that the prognostic effect of Th, Tc, and B cells in the tumor microenvironment is modulated by the nearby M2 macrophages. The proposed new method proposed can be readily applied to all single-cell spatial data for revealing functional impact of immune cell interactions.
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肺腺癌近端 M2 巨噬细胞决定浸润免疫细胞的预后效果
肿瘤微环境(TME)中免疫细胞的空间排列及其相互作用在癌症的发生和发展过程中起着至关重要的作用。成像质谱细胞术(IMC)等一些先进技术以单细胞分辨率提供了肿瘤微环境的免疫学景观。在本研究中,我们根据单细胞空间数据开发了一种量化不同细胞类型之间空间接近性的新方法。通过对 416 例肺部腺癌患者的 IMC 数据使用这种方法,我们发现与免疫细胞密度和分数等传统特征相比,不同细胞类型之间的邻近性与患者预后的相关性更高。与之前的报告一致,我们的研究结果验证了 T 辅助细胞(Th)和 B 细胞与癌细胞的接近度与生存益处相关。更重要的是,我们发现 M2 巨噬细胞接近多种免疫细胞与不良预后有关。当 Th/B 细胞被分层为 M2 远端和 M2 近端时,前一类 Th/B 细胞的丰度而非后一类 Th/B 细胞的丰度与患者生存率的提高相关。此外,M2-远端和M2-近端细胞毒性T细胞(Tc)的数量分别与预后良好和预后不良相关。我们的研究结果表明,肿瘤微环境中 Th、Tc 和 B 细胞的预后效应受附近 M2 巨噬细胞的调节。所提出的新方法可随时应用于所有单细胞空间数据,以揭示免疫细胞相互作用的功能影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Molecular Cancer
Molecular Cancer 医学-生化与分子生物学
CiteScore
54.90
自引率
2.70%
发文量
224
审稿时长
2 months
期刊介绍: Molecular Cancer is a platform that encourages the exchange of ideas and discoveries in the field of cancer research, particularly focusing on the molecular aspects. Our goal is to facilitate discussions and provide insights into various areas of cancer and related biomedical science. We welcome articles from basic, translational, and clinical research that contribute to the advancement of understanding, prevention, diagnosis, and treatment of cancer. The scope of topics covered in Molecular Cancer is diverse and inclusive. These include, but are not limited to, cell and tumor biology, angiogenesis, utilizing animal models, understanding metastasis, exploring cancer antigens and the immune response, investigating cellular signaling and molecular biology, examining epidemiology, genetic and molecular profiling of cancer, identifying molecular targets, studying cancer stem cells, exploring DNA damage and repair mechanisms, analyzing cell cycle regulation, investigating apoptosis, exploring molecular virology, and evaluating vaccine and antibody-based cancer therapies. Molecular Cancer serves as an important platform for sharing exciting discoveries in cancer-related research. It offers an unparalleled opportunity to communicate information to both specialists and the general public. The online presence of Molecular Cancer enables immediate publication of accepted articles and facilitates the presentation of large datasets and supplementary information. This ensures that new research is efficiently and rapidly disseminated to the scientific community.
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