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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1494806
This article is part of the Research Topic Immunotherapeutic Advances in Brain Tumors View all articles

ScRNA-seq Unveils the Functional Characteristics of Glioma-Associated Macrophages and the Regulatory Effects of Chlorogenic Acid on the Immune Microenvironment—A Study Based on Mouse Models and Clinical Practice

Provisionally accepted
Jiachen Wang Jiachen Wang 1,2Shenglan Li Shenglan Li 1,2Yuxiao Chen Yuxiao Chen 1,2,3Jinyi Chen Jinyi Chen 1,4Can Wang Can Wang 1Zhuang Kang Zhuang Kang 1Mengqian Huang Mengqian Huang 1,2Zehao Cai Zehao Cai 1,3Yuxiang Fan Yuxiang Fan 3Yanjie Lan Yanjie Lan 1,2Yumeng Yu Yumeng Yu 1,2Ruining Bai Ruining Bai 1,2Feng Chen Feng Chen 1Jian-Dong Jiang Jian-Dong Jiang 5Wenbin Li Wenbin Li 1,2*
  • 1 Beijing Tiantan Hospital, Capital Medical University, Beijing, China
  • 2 Capital Medical University, Beijing, Beijing Municipality, China
  • 3 Xuanwu Hospital, Capital Medical University, Beijing, Beijing Municipality, China
  • 4 Chinese Institute for Brain Research, Beijing (CIBR), Beijing, Beijing Municipality, China
  • 5 Chinese Academy of Medical Sciences and Peking Union Medical College, Dongcheng, Beijing Municipality, China

The final, formatted version of the article will be published soon.

    Glioma is the most common primary malignant brain tumor. Despite advances in surgical techniques and treatment regimens, the therapeutic effects of glioma remain unsatisfactory. Immunotherapy has brought new hope to glioma patients, but its therapeutic outcomes are limited by the immunosuppressive nature of the tumor microenvironment (TME). This study aimed to reveal the subpopulations and functional characteristics of tumor-associated macrophages (TAMs) to explore the regulatory effects of chlorogenic acid (CHA) on the immune microenvironment, and to investigate its potential for clinical application. In this study, CHA slowed tumor growth in model mice and extended the survival time of mice. ScRNA-seq analysis was conducted to elucidate the differentiation trajectories and functional characteristics of bone marrow-derived mono-macrophages (BMDMs) and microglia, revealing the regulatory effects of CHA on these two populations. It enhanced the antigen-presenting function of macrophages and T-cell immune activation-related gene expression, activated microglia through the JAK-STAT pathway, and improved the antitumor functions. A PPI and molecular docking model were constructed using the target prediction database, and the good affinity of CHA with STAT1 was confirmed. A case of a patient treated with CHA and survived for 5 years and 6 months was reviewed, who achieved partial remission (PR) after 9 months of treatment and remains alive without any new symptoms or toxic side effects. Our study revealed the subtypes and differentiation trajectories of TAMs. CHA significantly improved the immune microenvironment of glioma by modulating the function of BMDMs and microglia, demonstrating excellent antitumor effects. This study may provide new insights into targeting the regulation of TME and offer theoretical and practical support for the clinical application of CHA.

    Keywords: Chlorogenic acid (5-caffeoylquinic acid), Glioma, tumor-associated macrophages (TAM), Microglia, Immune microenvironment (IME), single-cell RNA (scRNA) sequencing, network pharmacology (NP)

    Received: 11 Sep 2024; Accepted: 19 Dec 2024.

    Copyright: © 2024 Wang, Li, Chen, Chen, Wang, Kang, Huang, Cai, Fan, Lan, Yu, Bai, Chen, Jiang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Wenbin Li, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.