Department of Dermatology, Course of Integrated Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
Department of Integrative Medicine for Allergic and Immunological Diseases, Course of Integrated Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
Front Immunol. 2021 Mar 30;12:651048. doi: 10.3389/fimmu.2021.651048. eCollection 2021.
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 (T), 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 T 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.
在皮肤 T 细胞淋巴瘤（CTCL）中，恶性 T 细胞来源于皮肤归巢性记忆 T 细胞，而良性 T 细胞也局限于同一皮肤损伤处。因此，评估 CTCL 中良性 T 细胞的表型特征和功能活性具有一定难度。三唾液酸神经节苷脂（GD3）是一种带有三个糖基的物质，其在实体恶性肿瘤细胞表面的表达逐渐增加，并且参与肿瘤的进展和肿瘤免疫抑制。然而，GD3 在 CTCL 中的作用尚未完全阐明。在本研究中，我们通过流式细胞术区分了 CTCL 皮肤损伤处的恶性和良性 T 细胞，并将其表型特征与来自对照皮肤标本的 T 细胞进行了比较。在 CTCL 皮肤损伤处，良性 T 细胞包括有限的驻留记忆 T 细胞（T 细胞），这些细胞在皮肤中处于静止状态，已知具有很强的抗肿瘤功能。良性 T 细胞表现出 Th17 特性降低，而恶性 T 细胞中 GD3 的表达较高。恶性 T 细胞中 GD3 的表达与良性 CD4 T 细胞产生的 IL-17A 呈负相关。恶性 T 细胞中的 GD3 被暗示与 CTCL 中 T 细胞分化的调节无关，可抑制良性 T 细胞的 Th17 活性。揭示 GD3 在抑制 CTCL 中 IL-17A 产生中的作用将有助于理解恶性肿瘤细胞抑制抗肿瘤活性的机制。
