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Updated: Mar 25, 2026

In Vitro Assay to Study Tumor-macrophage Interaction
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Chemokine-defined macrophage niches establish spatial organization of tumor immunity

Soubhik Ghosh1, Xin Li1, Kavita Rawat2

  • 1Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Hanover, NH, USA.

Nature Immunology
|March 24, 2026
PubMed

Insights

In lung cancer, distinct macrophage subsets and their locations dictate immune responses. Targeting specific macrophage recruitment pathways can enhance antitumor immunity and reduce immunosuppression.

Area of Science:

  • Immunology
  • Oncology
  • Cell Biology

Background:

  • Macrophages are key immune cells in solid tumors, but their roles in antitumor immunity are complex.
  • The interplay between macrophage lineage, spatial distribution, and immune function in lung cancer is not fully understood.

Purpose of the Study:

  • To investigate the functional specialization of distinct macrophage subsets in lung cancer.
  • To elucidate how macrophage spatial organization influences antitumor immunity and immunosuppression.
  • To identify therapeutic targets for modulating macrophage-driven immune responses in cancer.

Main Methods:

  • Single-cell and spatial transcriptomics were employed to profile macrophage populations.
  • Analysis of chemokine expression and cellular localization within the tumor microenvironment.
  • Assessment of immune cell recruitment and function in response to therapeutic interventions.

Main Results:

  • Two interstitial macrophage (IM) subsets (CD206hi and CD206lo) and recruited macrophages (recMacs) exhibit specialized functions.
  • Bronchovascular-associated CD206hi IMs promote tertiary lymphoid structure formation and lymphocyte recruitment, enhancing tumor control.
  • Tumor-resident Ccl2+ IMs recruit protumorigenic recMacs, while Ly6C+CD11b+ monocyte-derived dendritic cells (moDCs) in lymph nodes are immunosuppressive.
  • CCR5 blockade with maraviroc selectively inhibited antigen-bearing moDC migration, boosting dendritic cell-mediated antitumor immunity.

Conclusions:

  • Macrophage lineage and spatial compartmentalization are critical determinants of tumor immunity.
  • Targeting chemokine pathways and moDC migration offers strategies to overcome macrophage-driven immunosuppression.
  • Preserving protective IM functions while disrupting protumorigenic macrophage activities can enhance cancer immunotherapy.

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