REVIEW article
Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1659153
Role of Depression-Mediated Alterations in 1 Pro-Inflammatory Cytokines in Carcinogenesis
Provisionally accepted
- Affiliated Hospital of Jiangsu University, Zhenjiang, China
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Abstract: This review systematically examines the bidirectional relationship between 42 MDD and cancer, establishing chronic inflammation—orchestrated primarily by IL-6, 43 TNF-α, and IL-1β—as a critical biological link. It delineates the pathophysiological 44 mechanisms through which depression activates the HPA axis, induces gut microbiota 45 disruption, and provokes immune dysregulation, collectively fostering a systemic 46 pro-inflammatory state. This state further potentiates oncogenesis via sustained 47 activation of key signaling pathways—including JAK-STAT3, NF-κB, MAPK, and 48 PI3K/AKT—that drive tumor proliferation, angiogenesis, immune evasion, and 49 metastatic behavior. Although preclinical evidence is robust, clinical translation 50 remains impeded by significant heterogeneity in inflammatory 51 biomarkers—particularly IL-1β—and a stark deficiency of rigorous interventional 52 trials evaluating anti-cytokine biologics in cancer patients with comorbid depression. 53 Future research must therefore advance beyond mechanistic inquiry toward 54 inflammation-based patient stratification and prospective interventional studies, 55 aiming to validate multimodal strategies targeting the depression-inflammation-cancer 56 axis and ultimately propel psycho-oncology into an era of precision medicine.
Keywords: Cancer, Depression, IL-6, TNF-α, IL-1β
Received: 04 Jul 2025; Accepted: 26 Aug 2025.
Copyright: © 2025 Cao, Jiang, Chen and Dai. 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: Ping Chen, Affiliated Hospital of Jiangsu University, Zhenjiang, China
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