Foxp3 Expressing CD4+ CD25+ and CD8+CD28− T Regulatory Cells in the Peripheral Blood of Patients with Lung Cancer and Pleural Mesothelioma

Meloni, Federica; Morosini, Monica; Solari, Nicola; Passadore, Ileana; Nascimbene, Caterina; Novo, Monique; Ferrari, Marco; Cosentino, Marco; Marino, Franca; Pozzi, Ernesto; Fietta, A.

doi:10.1016/j.humimm.2005.11.005

Cited by 152 publications

(119 citation statements)

References 42 publications

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“…On day 3 postactivation, an early peak in FOXP3 expression was observed, which reduced to baseline level subsequently; this is in concordance with other reports demonstrating a transient FOXP3 expression shortly after activation and in itself did not indicate a conversion to regulatory T cells (28,29). Furthermore, Tcmra remained CD8ab 1 ; did not express significant TGF-b, PD-1, CD161, or high level of CD25; and were all in keeping with a nonregulatory and nonexhausted phenotype (30)(31)(32)(33)(34). The initial IL-10 peak at day 3 was similar to the transient FOXP3 expression postactivation; but the gradual rather than abrupt reduction until day 33 in Tcmra was unexpected.…”

Section: Discussionsupporting

confidence: 90%

The Road to Memory: An Early Rest for the Long Journey

Yit

et al. 2013

The Journal of Immunology

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Central memory T lymphocytes were reported to develop after acute but not chronic infection, which prompted this feasibility study on generating long-term CD8 T cells ex vivo, by applying a culture condition that simulates an acute infection. During 35 d of culture, naive T cells (CD45RA+, CD127+, CCR7+, CD62L+, CXCR3+) first developed into effector T cells (CD45RA+/−, CD127+/−, CCR7+/−, CD62L+, CXCR3+), followed by three intermediate stages: intermediate T cells 1 (CD45RO+, CD127+/−, CCR7+, CD62L+, CXCR3+), intermediate T cells 2 (CD45RO+, CD127−, CCR7−, CD62L+, CXCR3+), and intermediate T cells 3 (CD45RO+/−, CD127+, CCR7+, CD62L−, CXCR3+) before reverting to stable CD45RA+ central memory T cells (CD45RA+, CD127+, CCR7+, CD62L+, CXCR3+). If both anti-CD3 and the inflammatory milieu persisted beyond day 10, intermediate T cells 2 gradually developed into effector memory T cells (CD45RO+, CD127−, CCR7−, CD62L−, CXCR3+). Furthermore, intermediate T cells 2 or effector memory T cells, when cultured in persistent inflammatory cytokines devoid of anti-CD3, were converted to central memory T cells (CD45RO+, CCR7+, CD62L+). Overall, these results support ex vivo memory-like T lymphocyte production and favor a developmental pathway including both divergent and linear relationships.

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Section: Discussionsupporting

confidence: 90%

The Road to Memory: An Early Rest for the Long Journey

Yit

et al. 2013

The Journal of Immunology

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“…Peripheral blood of pleural mesothelioma patients Similar proportion of CD4 + CD25 + Treg cells found in both pleural mesothelioma patients and normal healthy controls, this was inferred to be a result of the disease being predominantly localised in nature [64] The Role of Regulatory T Cells in Mesothelioma…”

Section: Recruitment Of Treg Cells To Mesotheliomasmentioning

confidence: 83%

The Role of Regulatory T Cells in Mesothelioma

Ireland

Beilharz

2012

Cancer Microenvironment

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Malignant mesothelioma (MM) appears to be responsive to immunotherapy. The lack of complete tumour cure as a result of many immunotherapies tested to date suggests that the immune response to MM is complex and multi-parametric. Regulatory T (Treg) cells are prevalent within murine and human mesotheliomas with their removal shown to result in tumour growth inhibition and the release of anti-tumour effector T cells from immunosuppression. The targeting of immune checkpoints as treatments for various solid tumours has recently shown promise in clinical settings. In addition, synergy between chemotherapy and immunotherapy has been demonstrated for many cancers, including mesothelioma. Here we demonstrate Treg cells as critical mediators of the anti-tumour immune response to MM and potential targets for anti-tumour immunotherapy; though the timing and dosage of Treg cell manipulating immunotherapies need to be optimised.

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“…70 Accumulation of CD8 + CD28 − T cells is also quite common in different human cancers, such as lung 71 and colorectal. 72 Conceivably, infiltrating T cells undergo exhaustion more rapidly in the old skin and so contribute to malignant growth directly via secretion of pro-inflammatory cytokines 73 or indirectly by retarding the appropriate immune response to the growing tumor.…”

Section: Discussionmentioning

confidence: 99%

Age-associated inflammation connects RAS-induced senescence to stem cell dysfunction and epidermal malignancy

et al. 2015

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Aging is the single biggest risk factor for malignant transformation. Among the most common age-associated malignancies are non-melanoma skin cancers, comprising the most common types of human cancer. Here we show that mutant H-Ras activation in mouse epidermis, a frequent event in cutaneous squamous cell carcinoma (SCC), elicits a differential outcome in aged versus young mice. Whereas H-Ras activation in the young skin results in hyperplasia that is mainly accompanied by rapid hair growth, H-Ras activation in the aged skin results in more dysplasia and gradual progression to in situ SCC. Progression is associated with increased inflammation, pronounced accumulation of immune cells including T cells, macrophages and mast cells as well as excessive cell senescence. We found not only an age-dependent increase in expression of several pro-inflammatory mediators, but also activation of a strong anti-inflammatory response involving enhanced IL4/IL10 expression and immune skewing toward a Th2 response. In addition, we observed an age-dependent increase in the expression of Pdl1, encoding an immune suppressive ligand that promotes cancer immune evasion. Moreover, upon switching off oncogenic H-Ras activity, young but not aged skin regenerates successfully, suggesting a failure of the aged epidermal stem cells to repair damaged tissue. Our findings support an age-dependent link between accumulation of senescent cells, immune infiltration and cancer progression, which may contribute to the increased cancer risk associated with old age.

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Foxp3 Expressing CD4+ CD25+ and CD8+CD28− T Regulatory Cells in the Peripheral Blood of Patients with Lung Cancer and Pleural Mesothelioma

Cited by 152 publications

References 42 publications

The Road to Memory: An Early Rest for the Long Journey

The Road to Memory: An Early Rest for the Long Journey

The Role of Regulatory T Cells in Mesothelioma

Age-associated inflammation connects RAS-induced senescence to stem cell dysfunction and epidermal malignancy

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