Malignant and Benign T Cells Constituting Cutaneous T-Cell Lymphoma.

Shuichi Nakai,Rei Watanabe,Eiji Kiyohara

doi:10.3390/ijms222312933

Shuichi Nakai, Rei Watanabe + Show 1 more

Open Access

https://doi.org/10.3390/ijms222312933

Copy DOI

Abstract

Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of non-Hodgkin lymphoma, including various clinical manifestations, such as mycosis fungoides (MF) and Sézary syndrome (SS). CTCL mostly develops from CD4 T cells with the skin-tropic memory phenotype. Malignant T cells in MF lesions show the phenotype of skin resident memory T cells (TRM), which reside in the peripheral tissues for long periods and do not recirculate. On the other hand, malignant T cells in SS represent the phenotype of central memory T cells (TCM), which are characterized by recirculation to and from the blood and lymphoid tissues. The kinetics and the functional characteristics of malignant cells in CTCL are still unclear due, in part, to the fact that both the malignant cells and the T cells exerting anti-tumor activity possess the same characteristics as T cells. Capturing the features of both the malignant and the benign T cells is necessary for understanding the pathogenesis of CTCL and would lead to new therapeutic strategies specifically targeting the skin malignant T cells or benign T cells.

Highlights

Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of non-Hodgkin lymphoma
Considering other studies suggesting that CCL18 expression from macrophages and dendritic cells in the lesions is related to the severity and progression of CTCL [123,124], the benign Th2 cells within CTCL lesions might serve as pro-tumorigenic T cells and might be associated with the tumor progression of CTCL
tumor microenvironment (TME) in CTCL leads to the Th2-biased condition, affecting both malignant and benign T cells in the lesions, which would promote the expansion of malignant T cells and suppress the antitumor activities of benign T cells, sometimes making the distinction of these two fractions obscure

Summary

Introduction

Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of non-Hodgkin lymphoma. The clinical manifestation of CTCL is diverse. The most common type of CTCL is mycosis fungoides (MF), presenting with inflammatory skin lesions, such as erythematous patches, plaques, and tumors infiltrated by both malignant and benign T cells [1,2]. It is important to control the disease activity of the early-stage MF to prevent the progression to the advanced stage Another disease subtype, Sézary syndrome (SS), which is a rare and more aggressive type of CTCL, presents erythroderma, lymphadenopathy, and blood-circulating malignant T cells called Sézary cells from the early phase of disease [1,4]. Skin is a large barrier tissue which serves to prevent foreign antigens from entering the body Skin serves as both a structural and an immunological barrier, and healthy human skin contains an estimate of 20 billion memory T cells [5].

The Development of Skin TRM

The Function of Skin TRM

Distinguishment of Malignant and Benign T Cells in CTCL

Benign T Cells in CTCL

Tumor Microenvironment in CTCL

Conclusions