Tabriz University of Medical Sciences Advanced Pharmaceutical Bulletin 2228-5881 15 2 2025 07 05 M2 Macrophages-Based Immunotherapy: A New Therapeutic Approach in Liver Fibrosis 314 325 10.34172/apb.025.43855 EN Wahyu Widowati https://orcid.org/0000-0002-5401-7794 Adilah Hafizha Nur Sabrina Annisa Firdaus Sutendi Fadhilah Haifa Zahiroh Teresa Liliana Wargasetia Ita Margaretha Nainggolan Elham Rismani https://orcid.org/0000-0001-9997-3512 Massoud Vosough https://orcid.org/0000-0001-5924-4366 REVIEW 10.34172/apb.025.43855 2024 10 08 2025 06 01 Liver fibrosis (LF) is a pathological condition resulting from a chronic inflammatory response to multiple etiological factors, including viral infections, excessive alcohol consumption, and metabolic disorders. The important role of macrophages in this process, especially the M2 subtype, has attracted attention as a potential target for macrophage-based immunotherapy. M2 macrophages have anti-inflammatory and reparative properties that enable them to modulate the immune response and facilitate repairing damaged tissues. They participate in reducing fibrogenic features in term of gene expression and histological markers associated with LF. These cells phagocytose apoptotic cells and matrix components. M2 macrophage-based immunotherapy has shown great potential in ameliorating LF through mechanisms involving the IL-10/STAT3 and TGF-β/SMAD signaling pathways, which are essential in suppressing the pro-inflammatory response and supporting tissue regeneration. However, significant challenges such as individual resistance to therapy and the potential for promoting fibrosis suggest that further development and research are needed to optimize the safety and efficacy of this therapy in clinical applications. This study provides comprehensive insights into the role of M2 macrophages in LF and explores their potential as an innovative therapeutic approach in treating LF.