Abstract
In cutaneous T-cell lymphoma (CTCL), which arises from skin-tropic memory T cells, malignant T cells and benign T cells are confined in the same skin lesions. It is thus difficult to evaluate the phenotypic characteristics and functional activities of benign T cells in CTCL. Disialoganglioside with three glycosyl groups (GD3) is increasingly expressed on the surface of solid malignant tumor cells and takes part in tumor progression and suppression of tumor immunity. However, the role of GD3 in CTCL is not well-understood. In this study, the malignant and benign T cells in CTCL skin lesions were distinguished by flow cytometry and their phenotypic characteristics were compared with those of T cells from control skin specimens. In CTCL skin lesions, the benign T cells included limited resident memory T cells (TRM), which are sessile in skin and known to exert strong antitumor function. The benign T cells showed diminished Th17 property, and the expression of GD3 was high in the malignant T cells. The expression of GD3 in the malignant T cells inversely correlated with IL-17A production from the benign CD4 T cells. GD3 from the malignant T cells was implied to be involved in suppressing the Th17 activity of the benign T cells independent of the regulation of TRM differentiation in CTCL. Revealing the role of GD3 in inhibiting the production of IL-17A in CTCL would aid the understanding of the suppressive mechanism of the antitumor activity by malignant tumor cells.
Highlights
Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of non-Hodgkin lymphoma, in which malignant T cells primarily develop in the skin [1]
By comparing the expression levels of TRM markers CD69 and CD103 between benign T cells in cutaneous T-cell lymphoma (CTCL) lesions and control skin T cells, it was found that the ratio of CD69+CD103+ TRM was significantly lower in benign T cells from CTCL lesions than in control skin T cells both in CD4 and CD8 fractions (Figures 1A, B)
The expression of TRM markers was diverse in CTCL malignant T cells and this is in accordance with a previous report [19]
Summary
Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of non-Hodgkin lymphoma, in which malignant T cells primarily develop in the skin [1]. In the most major CTCL subtype (mycosis fungoides [MF]), the malignant cells represent resident memory T-cell (TRM) phenotype, which reside in the skin and do not recirculate, in the early stage [2]. CTCL skin lesions include the benign counterpart T cells, which are supposed to exert antitumor immunity. The Th2 cytokines from the malignant T cells in CTCL blood and skin lesions reportedly suppress the Th1 responses of the benign counterpart T cells [7]. The phenotypic characteristics and functional activity of benign T cells in CTCL skin lesions is not well-understood, since both malignant cells and benign counterparts are the same T cells and are confined in the same skin lesions, which makes it difficult to separately analyzing these populations
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