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World J Gastroenterol. Mar 14, 2026; 32(10): 115371
Published online Mar 14, 2026. doi: 10.3748/wjg.v32.i10.115371
Published online Mar 14, 2026. doi: 10.3748/wjg.v32.i10.115371
Growth differentiation factor 11 reprograms M2-like macrophages: Targeting immunometabolism for cancer therapy
Saeed Mohammadi, Mahmoud Darweesh, Ahmed Al-Harrasi, Natural and Medical Sciences Research Center, University of Nizwa, Nizwa 616, Ad Dakhiliyah, Oman
Author contributions: Mohammadi S was responsible for the conceptualization, investigation, and writing of the original draft; Darweesh M contributed to the study design, conducted the literature review, prepared the illustrations, and performed writing, review and editing; Al-Harrasi A provided supervision, and contributed to writing, review and editing.
Supported by the Oman Ministry of Higher Education, Research, and Innovation, No. BFP/RGP/HSS/24/015.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Corresponding author: Ahmed Al-Harrasi, PhD, Professor, Natural and Medical Sciences Re
Received: October 16, 2025
Revised: November 13, 2025
Accepted: January 6, 2026
Published online: March 14, 2026
Processing time: 138 Days and 12.9 Hours
Revised: November 13, 2025
Accepted: January 6, 2026
Published online: March 14, 2026
Processing time: 138 Days and 12.9 Hours
Core Tip
Core Tip: Growth differentiation factor 11 (GDF11) is a potent immunometabolic modulator that can reprogram pro-tumoral M2-like macrophages primarily studied in hepatocellular carcinoma. GDF11 reverses their dysfunctional metabolic state by activating Smad2/3 signaling, restoring mitochondrial oxidative phosphorylation (as indicated by increased oxygen consumption rate), and reducing immunosuppressive cellular cholesterol. This critical metabolic shift induces the production of anti-tumoral cytokines and reactive oxygen species, neutralizing tumor cell proliferation and migration. GDF11 could be a promising, mechanism-based strategy to flip the immune-suppressive microenvironment toward tumor destruction.