scholarly journals High IKZF2 Expression in Malignant T cells Promotes Disease Progression in Cutaneous T cell Lymphoma

2021 ◽  
Author(s):  
Bufang Xu ◽  
Fengjie Liu ◽  
Yumei Gao ◽  
Jingru Sun ◽  
Yingyi Li ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Disease Progression ◽  
Immune Escape ◽  
Cell Lymphoma ◽  
Malignant Cell ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Tumor Immune Escape ◽  
Malignant T Cells

Cutaneous T cell lymphoma is a generally indolent disease derived from skin-homing mature T cells. However, in advanced stages, CTCL may manifest as aggressive clinical behavior and lead to a poor prognosis. The mechanism of disease progression in CTCL remains unknown. Here, with a large clinical cohort, we identified that IKZF2, an essential transcription factor during T cell development and differentiation, showed stage-dependent overexpression in the malignant T cells in MF lesions. IKZF2 is specifically over-expressed in advanced-stage MF lesions, correlates with poor patient prognosis. Mechanistically, IKZF2 overexpression promotes CTCL progression via inhibiting malignant cell apoptosis and may contribute to tumor immune escape by downregulating MHC-II molecules and up-regulating the production of anti-inflammatory cytokine IL-10 by malignant T cells. These results demonstrate the important role of IKZF2 in high-risk CTCL and pave the way for future targeted therapy.

scholarly journals Galectin-1 inhibits the viability, proliferation, and Th1 cytokine production of nonmalignant T cells in patients with leukemic cutaneous T-cell lymphoma

Blood ◽  
2012 ◽  
Vol 119 (15) ◽  
pp. 3534-3538 ◽  
Author(s):  
Filiberto Cedeno-Laurent ◽  
Rei Watanabe ◽  
Jessica E. Teague ◽  
Thomas S. Kupper ◽  
Rachael A. Clark ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytokine Production ◽  
Immune Escape ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Tumor Immune Escape ◽  
T Cell Lymphomas ◽  
Malignant T Cells

Tumor-derived galectin-1 (Gal-1), a β-galactoside–binding S-type lectin, has been shown to encourage T-cell death and promote T cell–mediated tumor immune escape. In this report, we show that patients with leukemic cutaneous T-cell lymphomas, known to have limited complexity of their T-cell repertoires, have a predominant T helper type-2 (Th2) cytokine profile and significantly elevated plasma levels of Gal-1 compared with healthy controls. Circulating clonal malignant T cells were a major source of Gal-1. The conditioned supernatant of cultured malignant T cells induced a β-galactoside–dependent inhibition of normal T-cell proliferation and a Th2 skewing of cytokine production. These data implicate Gal-1 in development of the Th2 phenotype in patients with advanced-stage cutaneous T-cell lymphoma and highlight the Gal-1–Gal-1 ligand axis as a potential therapeutic target for enhancing antitumor immune responses.

scholarly journals Ectopic expression of a novel CD22 splice-variant regulates survival and proliferation in malignant T cells from cutaneous T cell lymphoma (CTCL) patients

Oncotarget ◽  
2015 ◽  
Vol 6 (16) ◽  
pp. 14374-14384 ◽  
Author(s):  
Ieva Bagdonaite ◽  
Hans H. Wandall ◽  
Ivan V. Litvinov ◽  
Claudia Nastasi ◽  
Jürgen C. Becker ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Splice Variant ◽  
Cell Lymphoma ◽  
Ectopic Expression ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Malignant T Cells

The Th9 Axis Reduces the Oxidative Stress and Promotes the Survival of Malignant T Cells in Cutaneous T-Cell Lymphoma Patients

2020 ◽  
Vol 18 (4) ◽  
pp. 657-668 ◽  
Author(s):  
Sushant Kumar ◽  
Bhavuk Dhamija ◽  
Soumitra Marathe ◽  
Sarbari Ghosh ◽  
Alka Dwivedi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
T Cells ◽  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Malignant T Cells

IL-32 supports the survival of malignant T cells in cutaneous T cell lymphoma

immuneACCESS ◽  
2021 ◽  
Author(s):  
KK Yu ◽  
NP Smith ◽  
SV Essien ◽  
JE Teague ◽  
P Vieyra-Garcia ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Malignant T Cells

scholarly journals JAK3 Is Expressed in the Nucleus of Malignant T Cells in Cutaneous T Cell Lymphoma (CTCL)

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 280
Author(s):  
Chella Krishna Vadivel ◽  
Maria Gluud ◽  
Sara Torres-Rusillo ◽  
Lasse Boding ◽  
Andreas Willerslev-Olsen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Rna Polymerase Ii ◽  
Nuclear Localization ◽  
Nuclear Export ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Malignant T Cells

Perturbation in JAK-STAT signaling has been reported in the pathogenesis of cutaneous T cell lymphoma (CTCL). JAK3 is predominantly associated with the intra-cytoplasmic part of IL-2Rγc located in the plasma membrane of hematopoietic cells. Here we demonstrate that JAK3 is also ectopically expressed in the nucleus of malignant T cells. We detected nuclear JAK3 in various CTCL cell lines and primary malignant T cells from patients with Sézary syndrome, a leukemic variant of CTCL. Nuclear localization of JAK3 was independent of its kinase activity whereas STAT3 had a modest effect on nuclear JAK3 expression. Moreover, JAK3 nuclear localization was only weakly affected by blockage of nuclear export. An inhibitor of the nuclear export protein CRM1, Leptomycin B, induced an increased expression of SOCS3 in the nucleus, but only a weak increase in nuclear JAK3. Importantly, immunoprecipitation experiments indicated that JAK3 interacts with the nuclear protein POLR2A, the catalytic subunit of RNA Polymerase II. Kinase assays showed tyrosine phosphorylation of recombinant human Histone H3 by JAK3 in vitro—an effect which was blocked by the JAK inhibitor (Tofacitinib citrate). In conclusion, we provide the first evidence of nuclear localization of JAK3 in malignant T cells. Our findings suggest that JAK3 may have a cytokine-receptor independent function in the nucleus of malignant T cells, and thus a novel non-canonical role in CTCL.

scholarly journals Malignant T cells express lymphotoxin α and drive endothelial activation in cutaneous T cell lymphoma

Oncotarget ◽  
2015 ◽  
Vol 6 (17) ◽  
pp. 15235-15249 ◽  
Author(s):  
Britt Lauenborg ◽  
Louise Christensen ◽  
Ulrik Ralfkiaer ◽  
Katharina L. Kopp ◽  
Lars Jønson ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lymphoma ◽  
Endothelial Activation ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Lymphotoxin Α ◽  
Malignant T Cells
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