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[This article belongs to Volume - 70, Issue - 1]
Published on : 2025-01-08 13:49:14
Article Code: AMJ-08-01-2025-12308
Title : Metabolic Reprogramming of Tumor-Associated Macrophages via ACLY Inhibition Reverses Immunosuppression in Ovarian Cancer
Author(s) : Dr. Laura Johnson, Dr. Michael Osei
Abstract :
Tumor-associated macrophages (TAMs) in the ovarian cancer ascites microenvironment exhibit protumoral M2
polarization driven by enhanced lipogenesis. Targeting ATP-citrate lyase (ACLY) with the specific inhibitor SB-204990
blocked histone acetylation at M2-associated gene loci (MRC1, CD163) while promoting inflammatory gene
expression. ACLY inhibition in TAMs restored CD8+ T-cell proliferation and interferon-γ production in co-culture
assays. In an orthotopic ovarian cancer model, combination of ACLY inhibition with anti-PD-L1 therapy achieved
complete tumor regression in 60% of mice versus 15% with monotherapy. Metabolic-immunologic crosstalk in TAMs
represents a targetable axis in ovarian cancer immunotherapy.