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

Yano, Hiroki; Ishida, Takashi; Inagaki, Atsushi; Ishii, Toshihiko; Kusumoto, Shigeru; Komatsu, Hirokazu; Iida, Shinsuke; Utsunomiya, Atae; Ueda, Ryuzo

doi:10.1002/ijc.22536

Cited by 86 publications

(71 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, Foxp3 is not only a selective marker for a subset of ATLL but is also a possible pathogenic pathway of leukemia. [24][25][26]33 Foxp3 directly controls Treg cell function by interacting with the transcription factor AML1 and the Runx1 to suppress IL-2 and IFN-g production, upregulate Treg cell-associated molecules and exert suppressive activity. 27,34,35 The new antisense strategy, RNA interference (RNAi), is one of the most potent.…”

Section: Discussionmentioning

confidence: 99%

Lentiviral-mediated Foxp3 RNAi suppresses tumor growth of regulatory T cell-like leukemia in a murine tumor model

Tsai

Suen²,

Chiang

2010

Gene Ther

View full text Add to dashboard Cite

Foxp3, a member of the forkhead transcription factor family, is a master gene that controls the development and function of CD4 CD25À effector cells stimulated with ConA. Moreover, lentiviral-mediated Foxp3 RNAi transduced into RL#1 cell or injected into the tumor showed suppressive effects on tumor growth and prolonged the survival of tumor-transplanted mice. However, this suppressive effect was abrogated in NOD-SCID mice transplanted with Lenti-Foxp3-siRNA-infected RL#1 cells. In conclusion, inhibiting Foxp3 gene expression by shRNAs effectively decreases tumor growth of Treg cell-like leukemia. The results may provide a novel strategy for future immunotherapy against cancers.

show abstract

Section: Discussionmentioning

confidence: 99%

Lentiviral-mediated Foxp3 RNAi suppresses tumor growth of regulatory T cell-like leukemia in a murine tumor model

Tsai

Suen²,

Chiang

2010

Gene Ther

View full text Add to dashboard Cite

show abstract

“…[20][21][22][23] Furthermore, recent studies have found that one of the functions of FOXP3( þ ) ATLL cells is a Treg-like suppressive activity. [23][24][25][26] Roncador et al 22 reported that FOXP3 was a specific marker of ATLL in peripheral T-cell lymphoma. 22 We can therefore assume that some ATLL cells express FOXP3 and may be derived from Tregs.…”

mentioning

confidence: 99%

The relationship of FOXP3 expression and clinicopathological characteristics in adult T-cell leukemia/lymphoma

et al. 2008

Self Cite

View full text Add to dashboard Cite

Adult T-cell leukemia/lymphoma is an aggressive malignant disease associated with regulatory T cells as discussed in some recent reports. We analyzed the expression of FOXP3, a key molecule of regulatory T cells, in adult T-cell leukemia/lymphoma and its association with clinicopathological features. Of 169 adult T-cell leukemia/lymphoma cases examined, 60 (36%) showed FOXP3 expression in lymphoma cells. Morphologically, 22 cases were classified as anaplastic large cell variant and 147 as pleomorphic cell variant. Only 1 (5%) of the anaplastic large cell variant cases and 59/147 (40%) of the pleomorphic cell variant cases expressed FOXP3. Epstein-Barr virus-infected cells were significantly more frequently found in FOXP3( þ ) cases (23/60; 38%) than in FOXP3(À) cases (12/109; 11%) (Po0.0001). Cytogenetic analysis showed that FOXP3( þ ) cases had simpler chromosomal abnormalities than FOXP3(À) cases. Clinically, FOXP3( þ ) and FOXP3(À) cases did not differ significantly in age distribution, clinical stage, lactate dehydrogenase and calcium in serum and overall survival. However, 8 of 34 FOXP3( þ ) cases suffered a severe infectious state, an indication of immunosuppression, while only 2 of 62 FOXP3(À) cases did so (Po0.005). FOXP3 expression in adult T-cell leukemia/lymphoma thus reflects morphological features and is clinically and pathologically associated with an immunosuppressive state.

show abstract

“…In hepatocellular carcinoma, high proportions of T regs within the liver are thought to precede the development of tumorigenesis and are associated with an unfavorable prognosis (22)(23)(24). Aggressive forms of adult T cell leukemia/lymphoma have been shown to up-regulate FoxP3 within the tumor cells themselves, conferring the ability of the tumor to actively suppress other lymphocytes (25). Bladder carcinomas have been found to be dominated by immunosuppressive regulatory T cells (26).…”

Section: Introductionmentioning

confidence: 99%

The Use of FoxP3 as a Biomarker and Prognostic Factor for Malignant Human Tumors

Schreiber

2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

Only since the early 21st century has it been proven that the immune system can actively defend the body against the development of malignant tumors. Escape from this process, termed immunosurveillance, has been shown to be required for the development of many tumors in both mice and humans, and may be a necessary prerequisite for the establishment of many malignancies. Serendipitously, an evolution in the understanding and characterization of immunosuppressor cells, regulatory T cells, has coincided with the establishment of tumor immunosurveillance. These two fields merged when it was found that the recruitment of regulatory T cells within tumors was a dominant mechanism tumors used to escape immunosurveillance. Regulatory T cells are specifically identified with antibodies which recognize the transcription factor, FoxP3. The presence of FoxP3+ cells within tumors has been shown to predict the prognosis, invasiveness, and metastatic ability of some tumors by modulating the ability of the immune system to target tumor cells. Furthermore, depletion of regulatory T cells from tumors could lead to the rejection of both early-and late-stage tumors by the host immune system. These findings suggest that the widespread use of FoxP3 as a biomarker should be explored for human tumors to enable physicians to make better decisions in oncologic care and to prepare the field for novel therapeutic agents directed at the elimination of regulatory T cells within tumors.

show abstract

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

Cited by 86 publications

References 21 publications

Lentiviral-mediated Foxp3 RNAi suppresses tumor growth of regulatory T cell-like leukemia in a murine tumor model

Lentiviral-mediated Foxp3 RNAi suppresses tumor growth of regulatory T cell-like leukemia in a murine tumor model

The relationship of FOXP3 expression and clinicopathological characteristics in adult T-cell leukemia/lymphoma

The Use of FoxP3 as a Biomarker and Prognostic Factor for Malignant Human Tumors

Contact Info

Product

Resources

About