scholarly journals Independent evolution of cutaneous lymphoma subclones in different microenvironments of the skin

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Aishwarya Iyer ◽  
Dylan Hennessey ◽  
Sandra O’Keefe ◽  
Jordan Patterson ◽  
Weiwei Wang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mycosis Fungoides ◽  
Cell Lymphoma ◽  
Cancer Prognosis ◽  
Epithelial Layer ◽  
Cutaneous T Cell Lymphoma ◽  
Hematogenous Seeding ◽  
High Degree ◽  
Branched Evolution

Abstract Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. Lesions of MF are formed by hematogenous seeding the skin with polyclonal (clonotypically diverse) neoplastic T-cells which accumulate numerous mutations and display a high degree of mutational, intratumoral heterogeneity (ITH). A characteristic but poorly studied feature of MF is epidermotropism, the tendency to infiltrate skin epithelial layer (epidermis) in addition to the vascularized dermis. By sequencing the exomes of the microdissected clusters of lymphoma cells from the epidermis and the dermis, we found that those microenvironments comprised different malignant clonotypes. Subclonal structure witnessed the independent mutational evolution in the epidermis and dermis. Thus, the epidermal involvement in MF could not be explained by gradual infiltration from the dermis but was caused by a separate seeding process followed by a quasi-neutral, branched evolution. In conclusion, tissue microenvironments shape the subclonal architecture in MF leading to “ecological heterogeneity” which contributes to the total ITH. Since ITH adversely affects cancer prognosis, targeting the microenvironment may present therapeutic opportunities in MF and other cancers.

scholarly journals Independent evolution of cutaneous lymphoma subclones in different microenvironments of the skin

2019 ◽  
Author(s):  
Aishwarya Iyer ◽  
Dylan Hennessey ◽  
Sandra O’Keefe ◽  
Jordan Patterson ◽  
Weiwei Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Phylogenetic Relationships ◽  
Cell Lymphoma ◽  
Cancer Prognosis ◽  
Driver Gene ◽  
Epithelial Layer ◽  
Cutaneous T Cell Lymphoma ◽  
Tumor Mass ◽  
Hematogenous Seeding ◽  
Branched Evolution

AbstractMycosis fungoides (MF) is the most common, yet incurable, cutaneous T-cell lymphoma. We have recently shown that the disease is initiated by hematogenous seeding the skin with clonotypically diverse neoplastic T-cells which proliferate accumulating numerous mutations and produce lesions of high intratumoral heterogeneity (ITH). A characteristic but a poorly studied feature of MF is epidermotropism, the tendency to infiltrate skin epithelial layer (epidermis) in addition to the vascularized dermis. By sequencing the exomes of the microdissected clusters of lymphoma cells from the epidermis and the dermis, we found that those microenvironments harbored different malignant clonotypes and exhibited different patterns of driver gene mutation. Phylogenetic relationships between cancer subclones witnessed to the independent mutational evolution in the epidermis and dermis. Thus, the invasion of MF to different skin layers does not occur by gradual infiltration of the expanding tumor mass, but is caused by separate seeding processes with different malignant clones that develop independently of one another via a neutral, branched evolution. In conclusion, tissue microenvironments shape the subclonal architecture in MF leading to “ecological heterogeneity” which contributes to the total ITH. Since ITH adversely affects cancer prognosis, targeting the microenvironment may present therapeutic opportunities in MF and other cancers.

Dermal dendrocytes and T-cells in canine mycosis fungoides. Support for an animal model of human cutaneous T-cell lymphoma

Cancer ◽  
1992 ◽  
Vol 70 (8) ◽  
pp. 2091-2098 ◽  
Author(s):  
David P. Fivenson ◽  
Elsa R. Beck ◽  
Robert W. Dunstan ◽  
Brian J. Nickoloff ◽  
Peter F. Moore
Keyword(s):  
Animal Model ◽  
T Cells ◽  
T Cell ◽  
Mycosis Fungoides ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma

scholarly journals Increased Expression of CTLA-4 in Malignant T Cells from Patients with Mycosis Fungoides – Cutaneous T-Cell Lymphoma

2006 ◽  
Vol 126 (1) ◽  
pp. 212-219 ◽  
Author(s):  
Henry K. Wong ◽  
Adam J. Wilson ◽  
Heather M. Gibson ◽  
Mikehl S. Hafner ◽  
Carrie J. Hedgcock ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mycosis Fungoides ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Malignant T Cells

scholarly journals Determining the immune environment of cutaneous T-cell lymphoma lesions through the assessment of lesional blood drops

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kan Torii ◽  
Yukinori Okada ◽  
Akimichi Morita
Keyword(s):  
T Cells ◽  
T Cell ◽  
Skin Biopsy ◽  
Mycosis Fungoides ◽  
Assessment Tool ◽  
Cell Lymphoma ◽  
Inflammatory Diseases ◽  
T Cell Lymphoma ◽  
Cell Populations ◽  
Cutaneous T Cell Lymphoma

AbstractDetailed analysis of the cells that infiltrate lesional skin cannot be performed in skin biopsy specimens using immunohistochemistry or cell separation techniques because enzyme treatments applied during the isolation step can destroy small amounts of protein and minor cell populations in the biopsy specimen. Here, we describe a method for isolating T cells from drops of whole blood obtained from lesions during skin biopsy in patients with cutaneous T-cell lymphoma. Lesional blood is assumed to contain lesional resident cells, cells from capillary vessels, and blood overflowing from capillary vessels into the lesion area. The lesional blood showed substantial increases in distinct cell populations, chemokines, and the expression of various genes. The proportion of CD8+CD45RO+ T cells in the lesional blood negatively correlated with the modified severity-weighted assessment tool scores. CD4+CD45RO+ T cells in the lesional blood expressed genes associated with the development of cancer and progression of cutaneous T-cell lymphoma. In addition, CD8+CD45RO+ T cells in lesional blood had unique T-cell receptor repertoires in lesions of each stage. Assessment of lesional blood drops might provide new insight into the pathogenesis of mycosis fungoides and facilitate evaluation of the treatment efficacy for mycosis fungoides as well as other skin inflammatory diseases.

Treatment of Mycosis Fungoides with Bexarotene Results in Remission of Diffuse Plane Xanthomas

2013 ◽  
Vol 17 (1) ◽  
pp. 52-54 ◽  
Author(s):  
Stamatis Gregoriou ◽  
Dimitris Rigopoulos ◽  
Christos Stamou ◽  
Vasiliki Nikolaou ◽  
George Kontochristopoulos
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mycosis Fungoides ◽  
Cell Lymphoma ◽  
Clinical Signs ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Cutaneous Lesions ◽  
Complete Clinical Remission

Background: Cutaneous xanthomas develop as a result of intracellular and dermal deposition of lipids in either hyper- or normolipidemic patients. Plane xanthomas may signal the presence of an underlying monoclonal gammopathy, chronic myelomonocytic leukemia, or cutaneous T-cell lymphoma. Investigators have suggested that xanthomatized T cells may result in induction of plane xanthomas. Methods: We report the case of a patient with mycosis fungoides (MF) and plane xanthomas who was treated with bexarotene for his MF. Results: Significant improvement in the clinical signs of MF was observed within 3 months. We also observed a substantial regression of the xanthomas after 5 months of treatment. Complete clinical remission of both the MF and xanthomas was obtained after 6 months. The patient was still free of xanthomas after 3 years of follow-up. Conclusion: Bexarotene led to the clearing of the cutaneous lesions of cutaneous T-cell lymphoma and plane xanthomas. This may be due to an effect of bexarotene on the aberrant T cells that may cause xanthomatization.

Locomotion of T cells from patients with cutaneous T-cell lymphoma (Sezary syndrome and mycosis fungoides)

1980 ◽  
Vol 50 (1) ◽  
pp. 195-201 ◽  
Author(s):  
Sudhir Gupta ◽  
Bijan Safai ◽  
Richard Edelson ◽  
Delphine Parrott ◽  
Robert Good
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mycosis Fungoides ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Sézary Syndrome ◽  
Sezary Syndrome ◽  
Cutaneous T Cell Lymphoma
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