The Role of Cytokines in Cutaneous T Cell Lymphoma: A Focus on the State of the Art and Possible Therapeutic Targets

Abstract

Cutaneous T cell lymphomas (CTCLs), encompassing mycosis fungoides (MF) and Sézary syndrome (SS), present a complex landscape influenced by cytokines and cellular responses. In this work, the intricate relationship between these inflammatory proteins and disease pathogenesis is examined, focusing on what is known at the clinical and therapeutic levels regarding the most well-known inflammatory mediators. An in-depth look is given to their possible alterations caused by novel immunomodulatory drugs and how they may alter disease progression. From this narrative review of the actual scientific landscape, Interferon-gamma (IFN-γ) emerges as a central player, demonstrating a dual role in both promoting and inhibiting cancer immunity, but the work navigates through all the major interleukins known in inflammatory environments. Immunotherapeutic perspectives are elucidated, highlighting the crucial role of the cutaneous microenvironment in shaping dysfunctional cell trafficking, antitumor immunity, and angiogenesis in MF, showcasing advancements in understanding and targeting the immune phenotype in CTCL. In summary, this manuscript aims to comprehensively explore the multifaceted aspects of CTCL, from the immunopathogenesis and cytokine dynamics centred around TNF-α and IFN-γ to evolving therapeutic modalities. Including all the major known and studied cytokines in this analysis broadens our understanding of the intricate interplay influencing CTCL, paving the way for improved management of this complex lymphoma.

A Narrative Review of the State of the Art of CCR4-Based Therapies in Cutaneous T-Cell Lymphomas: Focus on Mogamulizumab and Future Treatments

“…Specifically, Th2-type CD4 + T-cells, which are involved in allergic inflammatory disorders such as asthma, atopic dermatitis, and allergic rhinitis, express CCR4. On the other hand, the expression of CCR4 on Th1 cells, which are usually involved in cell-mediated immunity against infection, is related to a different immune mechanism and is relatively depleted [ 18 , 37 , 38 ]. The effectiveness of anti-CCL17 and anti-CCL22 antibodies in murine asthma models supports and strengthens a prevalent function for CCR4 on Th2 cells; as Th1 and Th2 responses have opposing functions, CCR4 antagonists act as adjuvants to steer the immune response toward a Th1-type response [ 39 , 40 , 41 ].…”

“…Compound [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , …”

“…Indeed, the therapeutic armamentarium has been implemented, and an approach has been formed based on the destruction of highly proliferating cells (i.e., the action of chemotherapy). The goal of the newly available drugs is not merely based on the induction of the apoptosis of the neoplastic cells, but it is also found on the reawakening of the host immune system to contrast CTCL [ 5 , 6 , 7 , 9 , 15 , 16 , 17 , 18 ].…”