Cell signaling in cutaneous T-cell lymphoma microenvironment: promising targets for molecular-specific treatment.

Autor: Rendón-Serna N; Instituto de Biología, Universidad de Antioquia, Medellin, Colombia.; Centro de Investigaciones Dermatológicas CIDERM, Facultad de Medicina, Universidad De Antioquia, Medellin, Colombia., Correa-Londoño LA; Centro de Investigaciones Dermatológicas CIDERM, Facultad de Medicina, Universidad De Antioquia, Medellin, Colombia., Velásquez-Lopera MM; Centro de Investigaciones Dermatológicas CIDERM, Facultad de Medicina, Universidad De Antioquia, Medellin, Colombia., Bermudez-Muñoz M; Instituto de Biología, Universidad de Antioquia, Medellin, Colombia.; Centro de Investigaciones Dermatológicas CIDERM, Facultad de Medicina, Universidad De Antioquia, Medellin, Colombia.
Jazyk: angličtina
Zdroj: International journal of dermatology [Int J Dermatol] 2021 Dec; Vol. 60 (12), pp. 1462-1480. Date of Electronic Publication: 2021 Apr 09.
DOI: 10.1111/ijd.15451
Abstrakt: Cutaneous T-cell lymphomas (CTCL) result from the infiltration and proliferation of a population of T cells in the skin, inducing changes in the activity of both T cells and surrounding skin cells. In the CTCL microenvironment, cell interactions mediated by cell signaling pathways are altered. Defining changes in cell signaling enables to understand T-cell deregulations in the CTCL microenvironment and thus the progression of the disease. Moreover, characterizing signaling networks activated in CTCL stages can lead to consider new molecular biomarkers and therapeutic targets. Focusing on mycosis fungoides (MF), the most frequent variant of CTCL, and Sézary syndrome (SS), its leukemic variant, this review highlights recent molecular and genetic findings revealing modifications of key signaling pathways involved in (1) cell proliferation, cell growth, and cell survival such as MAP kinases and PI3K/Akt; (2) immune responses derived from TCR, TLR, JAK/STAT, and NF-kB; and (3) changes in tissue conditions such as extracellular matrix remodeling, hypoxia, and angiogenesis. Alterations in these signaling networks promote malignant T-cell proliferation and survival, T-cell migration, inflammation, and suppression of immune regulation of malignant T cells, making a skin microenvironment that allows disease progression. Targeting key proteins of these signaling pathways, using molecules already available and used in research, in clinical trials, and with other disease indications, can open the way to different therapeutic options in CTCL treatment.
(© 2021 the International Society of Dermatology.)
Databáze: MEDLINE
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