Comprehensive characterization of early-programmed tumor microenvironment by tumor-associated macrophages reveals galectin-1 as an immune modulatory target in breast cancer

  • Theranostics. 2024 Jan 1;14(2):843-860. doi: 10.7150/thno.88917.
Hyewon Chung  1  2 ,  Park Gyu-Mi  1  3 ,  Yi Rang Na  4 ,  Yun-Sang Lee  5  6 ,  Hongyoon Choi  5  6 ,  Seung Hyeok Seok  1  3  7
Affiliations
  • 1. Macrophage Lab, Department of Microbiology and Immunology, and Institute of Endemic Disease, Seoul National University College of Medicine, Seoul 110-799, South Korea.
  • 2. Institute of Endemic Diseases, Seoul National University Medical Research Center (SNUMRC), Seoul, Republic of Korea.
  • 3. Department of Biomedical Sciences and Seoul National University College of Medicine, Seoul, Republic of Korea.
  • 4. Transdisciplinary Department of Medicine and Advanced Technology, Seoul National University Hospital, Seoul, South Korea.
  • 5. Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
  • 6. Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • 7. Cancer Research Institute, Seoul National University, Seoul, South Korea.
PMID: 38169569 DOI: 10.7150/thno.88917
Abstract

Background: In recent years, there has been considerable interest in the therapeutic targeting of tumor-associated macrophages (TAMs) to modulate the tumor microenvironment (TME), resulting in antitumoral phenotypes. However, key mediators suitable for TAM-mediated remodeling of the TME remain poorly understood. Methods: In this study, we used single-cell RNA Sequencing analyses to analyze the landscape of the TME modulated by TAMs in terms of a protumor microenvironment during early tumor development. Results: Our data revealed that the depletion of TAMs leads to a decreased epithelial-to-mesenchymal transition (EMT) signature in Cancer cells and a distinct transcriptional state characterized by CD8+ T cell activation. Moreover, notable alterations in gene expression were observed upon the depletion of TAMs, identifying Galectin-1 (Gal-1) as a crucial molecular factor responsible for the observed effect. Gal-1 inhibition reversed immune suppression via the reinvigoration of CD8+ T cells, impairing tumor growth and potentiating immune checkpoint inhibitors in breast tumor models. Conclusion: These results provide comprehensive insights into TAM-mediated early tumor microenvironments and reveal immune evasion mechanisms that can be targeted by Gal-1 to induce antitumor immune responses.

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