Mycosis Fungoides and Sézary Syndrome: Microenvironment and Cancer Progression

Abstract

Mycosis fungoides and Sézary syndrome are epidermotropic cutaneous lymphomas, and both of them are rare diseases. Mycosis fungoides is the most frequent primary cutaneous lymphoma. In about 25% of patients with mycosis fungoides, the disease may progress to higher stages. The pathogenesis and risk factors of progression in mycosis fungoides and Sézary syndrome are not yet fully understood. Previous works have investigated inter- and intrapatient tumor cell heterogeneity. Here, we overview the role of the tumor microenvironment of mycosis fungoides and Sézary syndrome by describing its key components and functions. Emphasis is put on the role of the microenvironment in promoting tumor growth or antitumor immune response, as well as possible therapeutic targets. We focus on recent advances in the field and point out treatment-related alterations of the microenvironment. Deciphering the tumor microenvironment may help to develop strategies that lead to long-term disease control and cure.

Keywords: Sézary syndrome; cutaneous T-cell lymphomas; microenvironment; mycosis fungoides.

Figure 1

Interactions in the tumor microenvironment in mycosis fungoides and Sézary syndrome. The figure shows selected interactions in the microenvironment of mycosis fungoides. Cells in orange represent macrophages, green keratinocytes, blue fibroblasts, red endothelial cells, cells marked with SZ represent tumor cutaneous T-cell lymphoma cells (Sézary cells), CD8 cytotoxic lymphocytes, and NK natural killer cells. Abbreviations: AMP—antimicrobial peptide, CCL—chemokine ligand, CXCL-chemokine X ligand, Il—interleukin, POSTN—periostin, TSLP—thymic stromal lymphopoietin, VEGF—vascular endothelial growth factor.

Figure 2

Main targetable immune checkpoints in mycosis fungoides and Sézary syndrome. The figure shows selected targetable immune checkpoints in mycosis fungoides and Sézary syndrome. Abbreviations: Eff-effector lymphocyte, Treg—regulatory T-cell, SZ—tumoral cell (Sézary cell), CD4—benign helper T-cell, Mac—macrophage, CCR—chemokine receptor, CXCR—chemokine X receptor, ICOS—inducible costimulatory receptor, PD-1—programmed death 1, PD-L1—programmed death ligand-1, SIRPα—signal regulatory protein α, TIGIT—T cell immunoreceptor with Ig and ITIM domains.