Evaluating the impact of using bone marrow-derived macrophages to turn early tumor sites into hot early tumor sites.

The impact of transforming an early tumor site into a hot early tumor site was evaluated using bone marrow-derived macrophages (BMDM) activated with IFN-γ and sCD40L in combination with Toll-like receptor (TLR) agonists (lipopolysaccharide (LPS), flagellin or R848). Not surprisingly, analysis of the activated BMDM revealed characteristics often ascribed to anti-tumor (M1) macrophages with production of nitrite and IL-12, as well as expression of Il-1b, Il-6, Tnf-a, Il-18, Ccl5, Cxcl9, Cxcl10, and Cxcl11. All treatments also led to a significant increase in MHC Class II or CD80 expression, but only BMDM activated with IFN-γ and LPS showed a significant increase in both MHC Class II and CD80 expression. Delivering these BMDM to early tumor sites slowed progression of three murine mammary carcinoma models (EMT6, 168, 4 T1). Depletion studies revealed that the anti-tumor activity was dependent upon CD8+ T cells and NK cells suggesting that expression of Ccl5, Cxcl9, Cxcl10, and/or Cxcl11 may be important for the in vivo function of the BMDM. Additionally, inhibiting G protein coupled receptor (GPCR) signaling in the BMDM ablated the anti-tumor activity suggesting that the anti-tumor activity may be dependent on the migratory ability of the BMDM. Collectively, these data show that creating hot early tumor sites by delivering anti-tumor BMDM can impact tumor growth by eliciting CD8+ T cells and NK cells, and that BMDM anti-tumor activity depends on GPCR-mediated signaling.

• Publication year

  2025

• Venue

  Cellular Immunology

• Publication date

  2025-11-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.cellimm.2025.105050PMID 41223817
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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