Targeting MARCO in combination with anti-CTLA-4 leads to enhanced melanoma regression and immune cell infiltration via macrophage reprogramming

Mar 13, 2025Journal for immunotherapy of cancer

Blocking MARCO and CTLA-4 together may improve melanoma shrinkage and immune cell response by changing macrophage behavior

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Abstract

ED31 enhanced the antitumor efficacy of anti-CTLA-4 in C57BL/6J mice bearing B16F10 or Pan02 tumors.

  • The combination of ED31 with anti-CTLA-4 significantly increased immune cell infiltration in the .
  • Mature conventional dendritic cell recruitment was notably enhanced by the addition of ED31 to anti-CTLA-4 treatment.
  • A shift to M1-pattern chemokines produced by macrophages was observed when ED31 was combined with anti-CTLA-4.
  • Depleting macrophages eliminated the increased immune cell infiltration and chemokine production, as well as the antitumor efficacy of the therapy.
  • Targeting MARCO may improve the effectiveness of anti-CTLA-4 therapy through the reprogramming of macrophages rather than their depletion.

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Key numbers

10 cells/cm
Increase in immune cell density
Total immune cells (CD45) density in the after treatment with ED31 and anti-CTLA-4.
n=35 (αCTLA-4+ED31) vs. n=15 (αCTLA-4 alone)
Survival comparison
Survival outcomes in mice treated with ED31 and anti-CTLA-4 versus anti-CTLA-4 alone.

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