ORIGINAL RESEARCH article

Front. Immunol.

Sec. Cancer Immunity and Immunotherapy

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1616514

This article is part of the Research TopicFormation and Remodeling of Immunological Niches in Tumors: Organ-Specific Mechanisms and Inflammatory Parallels: Volume IIView all 4 articles

Alveolar Macrophages Maintain Tissue Localization and Gain Enhanced Anti-Tumor Activity in Lewis Lung Carcinoma-Reprogrammed Lung Microenvironment

Provisionally accepted
Mengfei RenMengfei Ren1,2Jiaxiang DouJiaxiang Dou3Qian YueQian Yue1,3Hang YuHang Yu3,4Shijie WangShijie Wang5,6Jian WangJian Wang3,5,6*Tingting LiTingting Li7*Fengqi LiFengqi Li1,3,4,6*
  • 1School of Basic Medical Sciences, Center for Big Data and Population Health of IHM, Anhui Medical University, Hefei, China
  • 2Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei, China
  • 3Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei, Anhui Province, China
  • 4Center for Xin’an Medicine and Modernization of Traditional Chinese of IHM, Anhui University of Chinese Medicine Hefei, Hefei, China
  • 5Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
  • 6National Key Laboratory of Immune Response and Immunotherapy, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
  • 7Department of Clinical Laboratory, First Affiliated Hospital of Anhui Medical University, Hefei, China

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

Select one of your emails

You have multiple emails registered with Frontiers:

Notify me on publication

Please enter your email address:

If you already have an account, please login

You don't have a Frontiers account ? You can register here

The role of alveolar macrophages (AMs) in lung carcinogenesis has been extensively studied, yielding significant insights. However, the status of AMs in tumor-bearing lungs remains incompletely characterized. Using orthotopic Lewis Lung Carcinoma (LLC) mouse models, we found that tumors induced an inflammatory extra-tumoral lung microenvironment (ETLME), distinct from the immunosuppressive tumor microenvironment (TME). T cells with an exhaustion phenotype and tumor-associated macrophages (TAMs) mainly accumulated in the TME rather than the ETLME. Surprisingly, AMs were absent from the tumor lesions and remained in the lung tissues, but they displayed a more active dynamic balance between proliferation and death in ETLME. Furthermore, AMs presented an activated phenotype characterized by upregulation of CD11b and downregulation of Siglec-F, elevated expression of inflammatory genes, and enhanced phagocytic and efferocytotic activity. Notably, AMs in ETLME retained their lipid metabolism capacity and responsiveness to external stimuli. More importantly, LLC-experienced AMs display enhanced anti-tumor ability. These findings indicate that AMs maintain their tissue localization and functional integrity within the ETLME.

Keywords: Tumor Microenvironment, alveolar macrophages, lung inflammation, Lewis Lung Carcinoma, Extra-tumoral lung microenvironment

Received: 23 Apr 2025; Accepted: 24 Jun 2025.

Copyright: © 2025 Ren, Dou, Yue, Yu, Wang, Wang, Li 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:
Jian Wang, Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
Tingting Li, Department of Clinical Laboratory, First Affiliated Hospital of Anhui Medical University, Hefei, China
Fengqi Li, School of Basic Medical Sciences, Center for Big Data and Population Health of IHM, Anhui Medical University, Hefei, 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.

Supplementary Material