Cellular Interactions and Inflammation in the Pathogenesis of Cutaneous T-Cell Lymphoma

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2020 Oct 5

PMID 33015047

Citations 24

Authors

Veronica Stolearenco

Martin R J Namini

Siri S Hasselager

Maria Gluud

Terkild B Buus

Andreas Willerslev-Olsen

Niels Odum

Thorbjorn Krejsgaard

Affiliations

Soon will be listed here.

Abstract

Cutaneous T-cell lymphoma (CTCL) comprises a group of lymphoproliferative diseases characterized by the accumulation of malignant T cells in chronically inflamed skin lesions. In early stages, the disease presents as skin patches or plaques covering a limited area of the skin and normally follows an indolent course. However, in a subset of patients the cutaneous lesions develop into tumors and the malignant T cells may spread to the lymphatic system, blood and internal organs with fatal consequences. Despite intensive research, the mechanisms driving disease progression remain incompletely understood. While most studies have focused on cancer cell-intrinsic oncogenesis, such as genetic and epigenetic events driving malignant transformation and disease progression, an increasing body of evidence shows that the interplay between malignant T cells and non-malignant cells plays a crucial role. Here, we outline some of the emerging mechanisms by which tumor, stromal and epidermal interactions may contribute to the progression of CTCL with particular emphasis on the crosstalk between fibroblasts, keratinocytes and malignant T cells.

Citing Articles

Unveiling the Role of the Cellular Tumor Microenvironment and the Therapeutic Targets it Provides in Cutaneous T-Cell Lymphoma.

Chinas N, Kaliampou S, Nikolaou V Curr Oncol Rep. 2025; .

PMID: 40055269 DOI: 10.1007/s11912-025-01646-6.

Multi-Omic Data Integration Suggests Putative Microbial Drivers of Aetiopathogenesis in Mycosis Fungoides.

Licht P, Mailander V Cancers (Basel). 2024; 16(23).

PMID: 39682136 PMC: 11640326. DOI: 10.3390/cancers16233947.

Spatial cell graph analysis reveals skin tissue organization characteristic for cutaneous T cell lymphoma.

Sarkar S, Moller A, Hartebrodt A, Erdmann M, Ostalecki C, Baur A NPJ Syst Biol Appl. 2024; 10(1):143.

PMID: 39622929 PMC: 11612425. DOI: 10.1038/s41540-024-00474-x.

Targeting TAG-72 in cutaneous T cell lymphoma.

Evtimov V, Hammett M, Pupovac A, Nguyen N, Shu R, Van Der Weyden C Heliyon. 2024; 10(17):e36298.

PMID: 39263154 PMC: 11386021. DOI: 10.1016/j.heliyon.2024.e36298.

The skin microbiome stratifies patients with cutaneous T cell lymphoma and determines event-free survival.

Licht P, Dominelli N, Kleemann J, Pastore S, Muller E, Haist M NPJ Biofilms Microbiomes. 2024; 10(1):74.

PMID: 39198450 PMC: 11358159. DOI: 10.1038/s41522-024-00542-4.

References

Choi J, Goh G, Walradt T, Hong B, Bunick C, Chen K . Genomic landscape of cutaneous T cell lymphoma. Nat Genet. 2015; 47(9):1011-9. PMC: 4552614. DOI: 10.1038/ng.3356. View

Rook A, Zaki M, Wysocka M, Wood G, Duvic M, Showe L . The role for interleukin-12 therapy of cutaneous T cell lymphoma. Ann N Y Acad Sci. 2001; 941:177-84. DOI: 10.1111/j.1749-6632.2001.tb03721.x. View

Suzuki H, Boki H, Kamijo H, Nakajima R, Oka T, Shishido-Takahashi N . YKL-40 Promotes Proliferation of Cutaneous T-Cell Lymphoma Tumor Cells through Extracellular Signal-Regulated Kinase Pathways. J Invest Dermatol. 2019; 140(4):860-868.e3. DOI: 10.1016/j.jid.2019.09.007. View

Guenova E, Watanabe R, Teague J, DeSimone J, Jiang Y, Dowlatshahi M . TH2 cytokines from malignant cells suppress TH1 responses and enforce a global TH2 bias in leukemic cutaneous T-cell lymphoma. Clin Cancer Res. 2013; 19(14):3755-63. PMC: 3715586. DOI: 10.1158/1078-0432.CCR-12-3488. View

Mirvish E, Pomerantz R, Geskin L . Infectious agents in cutaneous T-cell lymphoma. J Am Acad Dermatol. 2010; 64(2):423-31. PMC: 3954537. DOI: 10.1016/j.jaad.2009.11.692. View

Miyagaki T, Sugaya M, Fujita H, Ohmatsu H, Kakinuma T, Kadono T . Eotaxins and CCR3 interaction regulates the Th2 environment of cutaneous T-cell lymphoma. J Invest Dermatol. 2010; 130(9):2304-11. DOI: 10.1038/jid.2010.128. View

Lindahl L, Willerslev-Olsen A, Gjerdrum L, Nielsen P, Blumel E, Rittig A . Antibiotics inhibit tumor and disease activity in cutaneous T-cell lymphoma. Blood. 2019; 134(13):1072-1083. PMC: 6764271. DOI: 10.1182/blood.2018888107. View

Nguyen V, Huggins R, Lertsburapa T, Bauer K, Rademaker A, Gerami P . Cutaneous T-cell lymphoma and Staphylococcus aureus colonization. J Am Acad Dermatol. 2008; 59(6):949-52. DOI: 10.1016/j.jaad.2008.08.030. View

Novelli S, Monter A, Garcia-Muret M, Martino R, Briones J, Sierra J . Discussion on the indication of allogeneic stem cell transplantation for advanced cutaneous T cell lymphomas. Int J Hematol. 2019; 110(4):406-410. DOI: 10.1007/s12185-019-02707-w. View

10.

Abeni D, Frontani M, Sampogna F, Sera F, Bolli S, Corona R . Circulating CD8+ lymphocytes, white blood cells, and survival in patients with mycosis fungoides. Br J Dermatol. 2005; 153(2):324-30. DOI: 10.1111/j.1365-2133.2005.06755.x. View

11.

Zhang Q, Raghunath P, Vonderheid E, Odum N, Wasik M . Lack of phosphotyrosine phosphatase SHP-1 expression in malignant T-cell lymphoma cells results from methylation of the SHP-1 promoter. Am J Pathol. 2000; 157(4):1137-46. PMC: 1850163. DOI: 10.1016/S0002-9440(10)64629-9. View

12.

Miyagaki T, Sugaya M, Suga H, Akamata K, Ohmatsu H, Fujita H . Angiogenin levels are increased in lesional skin and sera in patients with erythrodermic cutaneous T cell lymphoma. Arch Dermatol Res. 2012; 304(5):401-6. DOI: 10.1007/s00403-012-1238-0. View

13.

Hristov A, Tejasvi T, Wilcox R . Mycosis fungoides and Sézary syndrome: 2019 update on diagnosis, risk-stratification, and management. Am J Hematol. 2019; 94(9):1027-1041. DOI: 10.1002/ajh.25577. View

14.

Miyagaki T, Sugaya M, Fujita H, Saeki H, Tamaki K . Increased serum thymic stromal lymphopoietin levels in patients with cutaneous T cell lymphoma. Clin Exp Dermatol. 2009; 34(4):539-40. DOI: 10.1111/j.1365-2230.2008.02990.x. View

15.

Kim Y, Girardi M, Duvic M, Kuzel T, Link B, Pinter-Brown L . Phase I trial of a Toll-like receptor 9 agonist, PF-3512676 (CPG 7909), in patients with treatment-refractory, cutaneous T-cell lymphoma. J Am Acad Dermatol. 2010; 63(6):975-83. DOI: 10.1016/j.jaad.2009.12.052. View

16.

Rook A, Gelfand J, Gelfand J, Wysocka M, Troxel A, Benoit B . Topical resiquimod can induce disease regression and enhance T-cell effector functions in cutaneous T-cell lymphoma. Blood. 2015; 126(12):1452-61. PMC: 4573868. DOI: 10.1182/blood-2015-02-630335. View

17.

Gunther C, Zimmermann N, Berndt N, Grosser M, Stein A, Koch A . Up-regulation of the chemokine CCL18 by macrophages is a potential immunomodulatory pathway in cutaneous T-cell lymphoma. Am J Pathol. 2011; 179(3):1434-42. PMC: 3157276. DOI: 10.1016/j.ajpath.2011.05.040. View

18.

Fatima S, Siddiqui S, Usman Tariq M, Ishtiaque H, Idrees R, Ahmed Z . Mycosis Fungoides: A Clinicopathological Study of 60 Cases from a Tertiary Care Center. Indian J Dermatol. 2020; 65(2):123-129. PMC: 7059469. DOI: 10.4103/ijd.IJD_602_18. View

19.

Duvic M, Sherman M, Wood G, Kuzel T, Olsen E, Foss F . A phase II open-label study of recombinant human interleukin-12 in patients with stage IA, IB, or IIA mycosis fungoides. J Am Acad Dermatol. 2006; 55(5):807-13. DOI: 10.1016/j.jaad.2006.06.038. View

20.

Cedeno-Laurent F, Singer E, Wysocka M, Benoit B, Vittorio C, Kim E . Improved pruritus correlates with lower levels of IL-31 in CTCL patients under different therapeutic modalities. Clin Immunol. 2015; 158(1):1-7. PMC: 4420663. DOI: 10.1016/j.clim.2015.02.014. View