Dataset Information

Spatial Zonation of Pro- and Anti-inflammatory Tumor Macrophages After Anti-CD40

ABSTRACT: Seeking to understand how local tissue factors reinforce these divergent TAM phenotypes, we next investigated their spatial distribution in MC38 tumors following anti-CD40 treatment (days 6 and 8 post-inoculation). We performed high-definition spatial transcriptomics at a spatial resolution of ~2 µm on a formalin-fixed, paraffin-embedded (FFPE) section. H&E-staining revealed dense leukocyte infiltrates and a large necrotic core. Spatial mapping showed a clear partition in macrophage phenotypes. The peripheral zone was rich in antigen-presenting and proinflammatory macrophages, while antiinflammatory macrophages were concentrated close to the necrosis-proximal region. This pattern was consistent with the accumulation of Cd74+ and Cxcl9+ macrophages at the tumor edges and Spp1+ macrophages clustering toward the necrotic center. Cells co-expressing pro- and anti-inflammatory markers (Cxcl9+ / Cd74+ and Spp1+) were scattered between the single-positive populations, suggesting a continuous gradient of macrophage states driven by local stress.

ORGANISM(S): Mus musculus

PROVIDER: GSE290287 | GEO | 2025/10/10

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:The direct and indirect effects of targeting specific tumor-associated macrophage (TAM) subsets in cancer are not well-defined. TAM targeting strategies are frequently based on the ‘M1’ or ‘M2’ polarization categories, even as substantial data challenges this binary modeling of macrophage cell state. One molecule consistently referenced as a delineator of a putative immunosuppressive ‘M2’ state is the surface protein CD206. We thus made a novel conditional CD206 (Mrc1) knock-in mouse to specifically visualize and/or deplete CD206+ TAMs and assess their correspondence with pro-tumoral immunity. Early, but not late depletion of CD206+ macrophages and monocytes (here, ‘Mono/Macs’) led to an indirect loss of a key anti-tumor network of NK cells, conventional type I dendritic cells (cDC1) and CD8 T cells. Among myeloid cells, we found that the CD206+ TAMs are the primary producers of CXCL9, and able to differentially attract activated CD8 T cells. In contrast, a population of stress-responsive TAMs (“Hypoxic” or Spp1+) and immature monocytes, which lack CD206 expression and become prominent following early depletion, expressed markedly diminished levels of CXCL9. Those NK and CD8 T cells which enter CD206-depleted tumors express vastly reduced levels of the corresponding receptor Cxcr3, the cDC1-attracting chemokine Xcl1 and cDC1 growth factor Flt3l transcripts. Consistent with the loss of this critical network, early CD206+ TAM depletion decreased tumor control by antigen specific CD8 T cells in mice. Likewise, in humans, the CD206Replete, but not the CD206Depleted Mono/Mac gene signature correlated robustly with CD8 T cell, NK cell and stimulatory cDC1 gene signatures and transcriptomic signatures skewed towards CD206Replete Mono/Macs associated with better survival. Together, these findings negate the unqualified classification of CD206+ ‘M2-like’ macrophages as immunosuppressive and provide further evidence of the context-dependence of macrophage function in tumors.

Dataset Information

Spatial Zonation of Pro- and Anti-inflammatory Tumor Macrophages After Anti-CD40

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets