Growth differentiation factor 11 reprograms M2-like macrophages: Targeting immunometabolism for cancer therapy

doi:10.3748/wjg.v32.i10.115371

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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©Author(s) (or their employer(s)) 2026. No commercial re-use. See Permissions. Published by Baishideng Publishing Group Inc.

World J Gastroenterol. Mar 14, 2026; 32(10): 115371
Published online Mar 14, 2026. doi: 10.3748/wjg.v32.i10.115371

Table 1 Growth differentiation factor 11-mediated key immunometabolic mechanisms on M2-like macrophages

Feature/mechanism	M2-like macrophage state (baseline)	GDF11 treatment effect	Proposed anti-tumoral impact	Molecular markers/processes
Phenotype	Pro-tumoral, immune-suppressive	Reversal/de-polarization	Loss of pro-tumoral function and recognition	CD206 (decrease); anti-tumoral phenotype (increase)
Signaling	Varied/dependent on TME	Activation of canonical pathway	Transduction of immunometabolic shift signal	Smad2/3 activation
Mitochondria/energy	Low OXPHOS, high glycolysis	Restoration of OXPHOS	Enhanced energy metabolism for microbicidal function	Oxygen consumption rate (increase)
Lipid metabolism	High cholesterol/lipid accumulation	Reduction of lipid content	Interference with M2 maintenance and signaling	Total cellular cholesterol (decrease)
Redox state	Low microbicidal ROS	Increase in ROS	Induction of cytotoxic/inflammatory state	Reactive oxygen species (increase)

GDF11: Growth differentiation factor 11; TME: Tumor microenvironment; OXPHOS: Oxidative phosphorylation; ROS: Reactive oxygen species; CD: Cluster of differentiation.

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Citation: Mohammadi S, Darweesh M, Al-Harrasi A. Growth differentiation factor 11 reprograms M2-like macrophages: Targeting immunometabolism for cancer therapy. World J Gastroenterol 2026; 32(10): 115371
URL: https://www.wjgnet.com/1007-9327/full/v32/i10/115371.htm
DOI: https://dx.doi.org/10.3748/wjg.v32.i10.115371

Mohammadi S, Darweesh M, Al-Harrasi A. Growth differentiation factor 11 reprograms M2-like macrophages: Targeting immunometabolism for cancer therapy. World J Gastroenterol 2026; 32(10): 115371 [PMID: 41809448 DOI: 10.3748/wjg.v32.i10.115371]

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