FOXP3 expression accurately defines the population of intratumoral regulatory T cells that selectively accumulate in metastatic melanoma lesions

Ahmadzadeh, Mojgan; Felipe-Silva, Aloísio; Heemskerk, Bianca; Powell, Daniel J.; Wunderlich, John R.; Merino, María J.; Rosenberg, Steven A.

doi:10.1182/blood-2008-06-163048

Cited by 127 publications

(131 citation statements)

References 45 publications

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“…In fact, this clone has been shown the best currently available to study FOXP3 expression by immunohistochemistry [22]. More importantly, although the reactivity spectrum of FOXP3 is composed of T reg and may include small number of CD8 + cells, it has been recently shown that it is the most accurate single marker of T regs [53]. In this study, we observed FOXP3 + cell infiltration in most of the tumours.…”

Section: Discussionsupporting

confidence: 52%

An evaluation of the clinical significance of FOXP3+ infiltrating cells in human breast cancer

Mahmoud

Paish

Powe

et al. 2010

Breast Cancer Res Treat

159

115

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Section: Discussionsupporting

confidence: 52%

An evaluation of the clinical significance of FOXP3+ infiltrating cells in human breast cancer

Mahmoud

Paish

Powe

et al. 2010

Breast Cancer Res Treat

159

115

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“…In addition, it is likely that each mechanism plays a specific role in a given inflammatory tissue setting. It has been shown, for example, that Treg-derived IL-10 was mainly necessary for limitation of inflammation in the colon, lung, and skin (42), whereas recent data indicate that, at tumor sites, suppression is also due to the action of a subset of CD4 + CD25 + Foxp3 + T cells that release IL-10 and TGF-b1 (37,43).…”

Section: Discussionmentioning

confidence: 99%

LAG-3 Expression Defines a Subset of CD4+CD25highFoxp3+ Regulatory T Cells That Are Expanded at Tumor Sites

Camisaschi¹,

Casati²,

Rini³

et al. 2010

The Journal of Immunology

292

199

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“…Foxp3 in combination with cytokine profiles are useful markers to phenotypically define primary human Treg cells in tumor and inflammatory tissues (7,25,26). In contrast, Th17 cells represent a different inflammatory component and play an active role in inflammation (27)(28)(29)(30)(31)(32)(33)(34)(35) and cancer (36).…”

Section: Cd4mentioning

confidence: 99%

IL-17+ Regulatory T Cells in the Microenvironments of Chronic Inflammation and Cancer

Kryczek

Zhao

et al. 2011

The Journal of Immunology

233

212

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Foxp3+CD4+ regulatory T (Treg) cells inhibit immune responses and temper inflammation. IL-17+CD4+ T (Th17) cells mediate inflammation of autoimmune diseases. A small population of IL-17+Foxp3+CD4+ T cells has been observed in peripheral blood in healthy human beings. However, the biology of IL-17+Foxp3+CD4+ T cells remains poorly understood in humans. We investigated their phenotype, cytokine profile, generation, and pathological relevance in patients with ulcerative colitis. We observed that high levels of IL-17+Foxp3+CD4+ T cells were selectively accumulated in the colitic microenvironment and associated colon carcinoma. The phenotype and cytokine profile of IL-17+Foxp3+CD4+ T cells was overlapping with Th17 and Treg cells. Myeloid APCs, IL-2, and TGF-β are essential for their induction from memory CCR6+ T cells or Treg cells. IL-17+Foxp3+CD4+ T cells functionally suppressed T cell activation and stimulated inflammatory cytokine production in the colitic tissues. Our data indicate that IL-17+Foxp3+ cells may be “inflammatory” Treg cells in the pathological microenvironments. These cells may contribute to the pathogenesis of ulcerative colitis through inducing inflammatory cytokines and inhibiting local T cell immunity, and in turn may mechanistically link human chronic inflammation to tumor development. Our data therefore challenge commonly held beliefs of the anti-inflammatory role of Treg cells and suggest a more complex Treg cell biology, at least in the context of human chronic inflammation and associated carcinoma.

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FOXP3 expression accurately defines the population of intratumoral regulatory T cells that selectively accumulate in metastatic melanoma lesions

Cited by 127 publications

References 45 publications

An evaluation of the clinical significance of FOXP3+ infiltrating cells in human breast cancer

An evaluation of the clinical significance of FOXP3+ infiltrating cells in human breast cancer

LAG-3 Expression Defines a Subset of CD4+CD25highFoxp3+ Regulatory T Cells That Are Expanded at Tumor Sites

IL-17+ Regulatory T Cells in the Microenvironments of Chronic Inflammation and Cancer

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