FOXP3, a selective marker for a subset of adult T-cell leukaemia/lymphoma

FOXP3+ regulatory T cells: Current controversies and future perspectives

“…Support for the latter hypothesis is provided by recent data demonstrating that HTLV-1 infection of CD4 + CD25 -T cells from healthy donors induces a Treg phenotype by up-regulating CD25 protein, FOXP3 mRNA expression and TGF-b secretion in CD4 + cells [30]. While there have been reports of tumoural FOXP3 expression in an in vitro model of cutaneous T cell lymphoma [31], our data from primary lymphomas do not corroborate these findings, but indicate the presence of a high percentage of "natural" Treg in the skin of mycosis fungoides patients [27,29].…”

“…mAb (such as 236A/E7) that enable detection of the FOXP3 protein at the single cell level in routinely fixed tissue sections [14] have been used to demonstrate that FOXP3 expression in malignant lymphoma cells is restricted to a poor prognosis subpopulation of patients with adult T cell leukaemia/lymphoma (ATLL) [29]. ATLL has a CD4 + CD25 + phenotype and strong immunosuppressive function, yet it is unclear whether the causal infection by human T lymphotropic virus type 1 (HTLV-1) targets Treg or induces the regulatory phenotype.…”

Galectin-9 as a Predictive Marker for the Onset of Immune-Related Adverse Effects Associated with Anti-CCR4 MoAb Therapy in Patients with Adult T Cell Leukemia

“…ATL/ATLL cells were initially shown to be positive for mature T-cell surface antigens CD3, CD4, and CD25, and negative for CD8 with rare occasions of double negativity or double positivity for CD4 and CD8 (Hattori et al 1981;Hattori et al 1991). Subsequent studies on the nature of ATL/ATLL cells have shown that they are also positive for regulatory T-cell (Treg) markers, such as FoxP3 (Karube et al 2004;Roncador et al 2005) and the CC chemokine receptor 4 (CCR4) (Yoshie et al 2002). Moreover, several secreted (cytokine) and cell surface-associated (receptor) factors serve as important clues for monitoring the activity and prognosis of patients with ATL/ATLL (Yasuda et al 1988;Yamada et al 1996;Mori and Prager 1998).…”

Regulatory T‐cell function of adult T‐cell leukemia/lymphoma cells

“…Recently, several investigators including ourselves have reported that FOXP3, which is a master control gene for the development and function of CD4 1 CD25 1 naturally occurring regulatory T (Treg) cells, [2][3][4] is expressed in the tumor cells from a subset of patients with ATLL. [5][6][7][8][9][10] Furthermore, we and other investigators have reported that ATLL cells from most patients express CCR4, 11,12 and very recently, Hirahara et al reported that virtually all peripheral blood CD4 1 CD25 high Foxp3 1 Treg cells express high levels of CCR4. 13 Collectively, because most ATLL cells express both CD4 and CD25, 1 based on their phenotypic characteristics, these tumors might originate from CD4 1 CD25 1 FOXP3 1 CCR4 1 Treg cells.…”