REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1636839
This article is part of the Research TopicRegulators of the Immune-Tumor Microenvironment: A New Frontier for Cancer ImmunotherapyView all 20 articles
Macrophage Migration Inhibitory Factor (MIF) and the Tumor Ecosystem: A Tale of Inflammation, Immune Escape, and Tumor Growth
Provisionally accepted
Rana A. Youness1*
Noha Mousaad Elemam2
Abdelhamid M Abdelhamid3
Adham H Mohamed4
Lolowa M Elsherbiny1Asmaa Ramzy5
Reem Amr Assal6*- 1German International University, Cairo, Egypt
- 2Clinical Sciences Department, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
- 3Nile University, Sheikh Zayed City, Egypt
- 4Cairo University, Giza, Egypt
- 5Children's Cancer Hospital Egypt 57357, Cairo, Egypt
- 6Department of Pharmacology and Toxicology, Heliopolis University for Sustainable Development, Cairo, Egypt
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Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine with a pivotal role in immune regulation, inflammation, and tumorigenesis. Originally identified as a T cell-derived factor inhibiting macrophage migration, MIF has since been recognized as a key player in the progression of a wide range of solid tumors. This comprehensive review traces the historical discovery and evolving understanding of MIF, highlighting its structural features, receptor interactions, and intracellular signaling mechanisms. The review also explores the molecular mechanisms of MIF involvement in tumor pathogenesis through promoting proliferation, angiogenesis, immune evasion, and metastasis. Special focus is given to MIF interplay with several oncogenic pathways, modulation of the tumor microenvironment, and its dual role in both autocrine and paracrine signaling within tumors. The review also discusses emerging insights into MIF's involvement in therapeutic resistance and its potential as a diagnostic biomarker and therapeutic target. By consolidating current knowledge, the authors aim to provide a detailed perspective on MIF's multifaceted role in solid tumors and to outline future directions for research and clinical intervention.
Keywords: Macrophage Migration Inhibitory Factor (MIF), Immune Regulation, solid tumors, Inflammatory mediator, Tumor Microenvironment
Received: 28 May 2025; Accepted: 19 Sep 2025.
Copyright: © 2025 Youness, Elemam, Abdelhamid, Mohamed, Elsherbiny, Ramzy and Assal. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Rana A. Youness, rana.youness21@gmail.com
Reem Amr Assal, reem.assal@gmail.com
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