The Multifaceted Role of the Il-2 Cytokine Family in Melanoma: Mechanisms, Therapeutic Implications, and Immune Modulation Publisher Pubmed



M Daghaighei MONA ; S Dodge SAMANEH ; S Bolandi SOHEIL ; B Youssef BOUTROS ; N Attarde NIKET ; M Maddahi MOEIN ; M Mostofi MARYAM ; R Morovatshoar REZA ; M Mostafavi MEHRNAZ ; D Majid DEJBAKHT
Source: Journal of Immunology Research Published:2025

Abstract

Background and Objective: Melanoma is a complex malignancy where the interplay between immune cells, cytokines, and the tumor microenvironment (TME) significantly influences disease progression and patient outcomes. This review explores the involvement of the interleukin-2 (IL-2) cytokine family in both the development and therapeutic approaches for melanoma. Methods: A narrative literature review was conducted, synthesizing findings from studies on immune cell behavior, cytokine functions, and their implications in melanoma and other cancers. This narrative review emphasizes the roles of immune cells and cytokines in both promoting and inhibiting tumor growth. Results: Neutrophils, influenced by tumor-derived cytokines, can adopt phenotypes that either inhibit or promote tumor growth. B cells in the TME often correlate with better survival, although their regulatory forms can suppress immune responses. Tissue-resident memory T cells (TRM cells) are crucial for antitumor immunity, particularly in response to immune checkpoint inhibitors (ICIs). Dendritic cells (DCs) are vital for antigen presentation, yet their function can be compromised in melanoma. Macrophages frequently support tumor growth through immunosuppressive actions. The IL-2 cytokine family, including IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21, plays diverse roles in immune regulation. These cytokines are involved in T-cell proliferation, B-cell differentiation, and modulation of other immune responses, influencing both tumor progression and the effectiveness of immunotherapies. Conclusions: Immune cells and cytokines are pivotal in the pathogenesis, progression, and immunotherapy of melanoma. Understanding their complex roles offers insights into potential therapeutic strategies, highlighting the importance of targeted immunotherapies in treating melanoma and possibly other cancers. Additional studies are required to clarify the precise mechanisms and interactions occurring within the TME to enhance treatment strategies. © 2025 Elsevier B.V., All rights reserved.