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Updated: Jan 15, 2026

In Vitro Assay to Study Tumor-macrophage Interaction
Published on: August 1, 2019
Targeting complex IV to alter the tumor microenvironment and boost macrophage antitumor immunity
Thomas Pfefer1, Luke A J O'Neill1
1School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin D02 R590, Ireland.
None:
Clark et al. showcase that interferons (IFNs) trigger a functional reprogramming of tumor-associated macrophages (TAMs) by downregulating NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4 (NDUFA4), a key subunit of mitochondrial complex Ⅳ. This drives a transition from protumor TAMs to antitumor IFN-associated TAMs (IFN-TAMs) through activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. This mechanism can be leveraged to boost antitumor immunity and improve responses to immune checkpoint blockade.
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