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Review
. 2021 Nov 29;22(23):12933.
doi: 10.3390/ijms222312933.

Malignant and Benign T Cells Constituting Cutaneous T-Cell Lymphoma

Shuichi Nakai  1   2 , Eiji Kiyohara  1 , Rei Watanabe  1   3
Affiliations
Review

Malignant and Benign T Cells Constituting Cutaneous T-Cell Lymphoma

Shuichi Nakai et al. Int J Mol Sci. .

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.

Keywords: benign T cells; cutaneous T-cell lymphoma; malignant T cells; mycosis fungoides; skin resident memory T cells.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The cell-surface molecules characteristic of the malignant T cells found in mycosis fungoides (MF) and Sézary syndrome (SS). (A) The malignant T cells in a well-demarcated patch or plaque lesions of MF typically show the resident memory T cells (TRM) phenotype with CD69 and CD103 expression. (B) The malignant T cells found in diffuse erythema of SS typically show the central memory T cells (TCM) phenotype with CCR7 and CD62L expression. Created by BioRender.com.
Figure 2
Figure 2
Tumor microenvironment in CTCL. The recruitment and proliferation of malignant T cells are promoted by chemokines and cytokines from the tumor-constituting cells, including TAM, CAF, dendritic cells, keratinocytes, and Th2 cells. IL-15 from the malignant T cells works in the autocrine manner too. Inflammatory synapses are formed among dendritic cells, benign Th2, and malignant T cells and contribute to Th2-biased microenvironment and tumor progression. Benign Th1 and Tc1 cells exert antitumor effects by producing IFNγ and granzymes, while they are suppressed by Th2 cytokines, such as IL-4 and IL-13, which benign Th2 and malignant T cells produce. Tumor-promoting molecules are represented in red, and tumor-suppressive molecules are indicated in blue.
See this image and copyright information in PMC

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References

    1. Willemze R., Cerroni L., Kempf W., Berti E., Facchetti F., Swerdlow S.H., Jaffe E.S. The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas. Blood. 2019;133:1703–1714. doi: 10.1182/blood-2018-11-881268. - DOI - PMC - PubMed
    1. Clark R.A., Shackelton J.B., Watanabe R., Calarese A., Yamanaka K., Campbell J.J., Teague J.E., Kuo H.P., Hijnen D., Kupper T.S. High-scatter T cells: A reliable biomarker for malignant T cells in cutaneous T-cell lymphoma. Blood. 2011;117:1966–1976. doi: 10.1182/blood-2010-05-287664. - DOI - PMC - PubMed
    1. Agar N.S., Wedgeworth E., Crichton S., Mitchell T.J., Cox M., Ferreira S., Robson A., Calonje E., Stefanato C.M., Wain E.M., et al. Survival outcomes and prognostic factors in mycosis fungoides/Sezary syndrome: Validation of the revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer staging proposal. J. Clin. Oncol. 2010;28:4730–4739. doi: 10.1200/JCO.2009.27.7665. - DOI - PubMed
    1. Najidh S., Tensen C.P., van der Sluijs-Gelling A.J., Teodosio C., Cats D., Mei H., Kuipers T.B., Out-Luiting J.J., Zoutman W.H., van Hall T., et al. Improved Sezary cell detection and novel insights into immunophenotypic and molecular heterogeneity in Sezary syndrome. Blood. 2021 doi: 10.1182/blood.2021012286. - DOI - PubMed
    1. Clark R.A., Chong B., Mirchandani N., Brinster N.K., Yamanaka K., Dowgiert R.K., Kupper T.S. The vast majority of CLA+ T cells are resident in normal skin. J. Immunol. 2006;176:4431–4439. doi: 10.4049/jimmunol.176.7.4431. - DOI - PubMed