About this Research Topic
Cytokines and their receptors play a major role in the pathogenesis and pathophysiology of human lymphomas. IL-13 is a growth factor for tumor cells in mycosis fungoides and Hodgkin lymphoma and is produced by tumor cells of breast implant associated anaplastic large cell lymphoma. TGF-beta is a negative regulator of both T- and B-cell lymphomas. IL-6 contributes to the aggressiveness and systemic symptoms of diffuse large B-cell lymphoma and Hodgkin's lymphoma. The microenvironment of Hodgkin's lymphoma is affected by IL-5 which recruits eosinophiles and by TARC/CCL17 which attract CD4+ T-lymphocytes. CCR4, the receptor for TARC, is a target for therapy of cutaneous T-cell lymphomas. Increased amounts of IL-1, IL-3, IL-4, IL-8, GM-CSF, TNF-alpha, TGF-beta, and LIF have been demonstrated in lesions of Langerhans cell histiocytosis. The IL-1R pathway is a potential target in primary cutaneous anaplastic large cell lymphomas.
CD30/TNFRSF8 is a consistent biomarker for classical Hodgkin's and anaplastic large cell lymphoma and is a popular target for relapse of these lymphomas. CD30 is also expressed in large cell transformed mycosis fungoides, primary effusion lymphoma, extra-nodal NK/T-cell lymphomas, EBV+ diffuse large B-cell lymphomas, and mastocytosis.
In the context of skin lymphomagenesis, a type 2 immune profile is typical of mycosis fungoides and Sézary syndrome, the most frequent subtypes of cutaneous T-cell lymphoma. Key cytokines of type 2 immunity—including IL-4, IL-13, IL-31, and the thymic stromal lymphopoietin—have been implicated to different degrees in the pathogenesis of these cutaneous entities as well as in their associated pruritus. In-depth understanding on the contribution of these cytokines to the onset and progression of cutaneous T-cell lymphomas may provide a rationale for the investigation of targeted therapeutic agents in this specific setting. Moreover, cutaneous B-cell lymphomas constitute an overall rare subgroup and a current area of unmet therapeutic need. Lymphoid tissue-associated chemokines, as well as vascular addressins, are crucial regulators in both physiologic homing of B-cells and in B-cell lymphomagenesis in the skin. These signals support the development of indolent subtypes of primary cutaneous marginal zone lymphoma and primary cutaneous follicle center lymphoma by interacting with surface chemokine receptors, such as CXCR4 or CXCR5 receptors, that are broadly expressed across B cells in these disorders.
Studies comparing indolent and aggressive subtypes of cutaneous B-cell lymphoma as well as these cutaneous entities and their nodal counterparts are needed to identify molecular differences that may account for the peculiar and mostly favorable behavior associated to cutaneous lymphomas. Advancing our pathogenetic understanding in this setting may provide potential targets for drug discovery in the setting of lymphoproliferative disorders in the skin and beyond.
The specialized role of cytokines and their ligands highlights their value as biomarkers for the diagnosis, monitoring, therapy, and prognosis of many lymphomas. We hope to expand this knowledge in many, perhaps unexpected, directions through this Research Topic.
Topic Editor Dr. Alvise Sernicola has performed consultancies for Sanofi, Pierre Fabre, and L’Oréal. All other Topic Editors declare no competing interests with regards to the Research Topic subject.
CD30/TNFRSF8 is a consistent biomarker for classical Hodgkin's and anaplastic large cell lymphoma and is a popular target for relapse of these lymphomas. CD30 is also expressed in large cell transformed mycosis fungoides, primary effusion lymphoma, extra-nodal NK/T-cell lymphomas, EBV+ diffuse large B-cell lymphomas, and mastocytosis.
In the context of skin lymphomagenesis, a type 2 immune profile is typical of mycosis fungoides and Sézary syndrome, the most frequent subtypes of cutaneous T-cell lymphoma. Key cytokines of type 2 immunity—including IL-4, IL-13, IL-31, and the thymic stromal lymphopoietin—have been implicated to different degrees in the pathogenesis of these cutaneous entities as well as in their associated pruritus. In-depth understanding on the contribution of these cytokines to the onset and progression of cutaneous T-cell lymphomas may provide a rationale for the investigation of targeted therapeutic agents in this specific setting. Moreover, cutaneous B-cell lymphomas constitute an overall rare subgroup and a current area of unmet therapeutic need. Lymphoid tissue-associated chemokines, as well as vascular addressins, are crucial regulators in both physiologic homing of B-cells and in B-cell lymphomagenesis in the skin. These signals support the development of indolent subtypes of primary cutaneous marginal zone lymphoma and primary cutaneous follicle center lymphoma by interacting with surface chemokine receptors, such as CXCR4 or CXCR5 receptors, that are broadly expressed across B cells in these disorders.
Studies comparing indolent and aggressive subtypes of cutaneous B-cell lymphoma as well as these cutaneous entities and their nodal counterparts are needed to identify molecular differences that may account for the peculiar and mostly favorable behavior associated to cutaneous lymphomas. Advancing our pathogenetic understanding in this setting may provide potential targets for drug discovery in the setting of lymphoproliferative disorders in the skin and beyond.
The specialized role of cytokines and their ligands highlights their value as biomarkers for the diagnosis, monitoring, therapy, and prognosis of many lymphomas. We hope to expand this knowledge in many, perhaps unexpected, directions through this Research Topic.
Topic Editor Dr. Alvise Sernicola has performed consultancies for Sanofi, Pierre Fabre, and L’Oréal. All other Topic Editors declare no competing interests with regards to the Research Topic subject.
Keywords: Cytokines, chemokines, lymphoma, T-cell lymphomas, B-cell lymphomas, lymphomagenesis, lymphoproliferative disorders
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