Foxp3+ Regulatory T Cells and Natural Killer Cells Distinctly Infiltrate Primary Tumors and Draining Lymph Nodes in Pulmonary Adenocarcinoma

Schneider, Thomas; Kimpfler, Silvia; Warth, Arne; Schnabel, Philipp A.; Dienemann, Hendrik; Schadendorf, Dirk; Hoffmann, Hans; Umansky, Viktor

doi:10.1097/jto.0b013e31820b80ca

Cited by 69 publications

(52 citation statements)

References 28 publications

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“…Tumor infiltration by Tregs, near-to-invariably detected by the immunohistochemical detection of FOXP3 + lymphocytes, has been associated with poor prognosis in cohorts of patients affected by multiple distinct neoplasms, including Hodgkin lymphoma, melanoma as well as breast, gastric and ovarian carcinoma [29, [91][92][93][94]. In line with these results, it has been shown that clinical response to chemotherapy is often associated with a reduction in TITregs and the recruitment of intratumoral CD8 + T cells [95].…”

Section: Clinical Significance Of Intratumoral Tregsmentioning

confidence: 90%

Tumor-Infiltrating Regulatory T Cells: Phenotype, Role, Mechanism of Expansion In Situ and Clinical Significance

Tanchot

Terme

Péré

et al. 2012

Cancer Microenvironment

115

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In immunocompetent individuals, the immune system initially eradicates potentially tumorigenic cells as they develop, a capacity that is progressively lost when malignant cells acquire alterations that sustain immunosubversion and/or immunoevasion. One of the major mechanisms whereby cancer cells block antitumor immune responses involves a specific class of immunosuppressive T cells that-in the vast majority of cases-express the Forkhead box P3 (FOXP3) transcription factor. Such FOXP3 + regulatory T cells (Tregs) accumulate within neoplastic lesions as a result of several distinct mechanisms, including increased infiltration, local expansion, survival advantage and in situ development from conventional CD4 + cells.

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Section: Clinical Significance Of Intratumoral Tregsmentioning

confidence: 90%

Tumor-Infiltrating Regulatory T Cells: Phenotype, Role, Mechanism of Expansion In Situ and Clinical Significance

Tanchot

Terme

Péré

et al. 2012

Cancer Microenvironment

115

View full text Add to dashboard Cite

show abstract

“…Schneider et al (30) reported FoxP3 + Treg accumulation and a decrease in the natural killer cells in the center of adenocarcinomas, whereas squamous cell carcinomas displayed less profound accumulation of Tregs. We demonstrated that the number of cCD4 + lymphocytes in adenocarcinomas was significantly higher compared to that in other histological types.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of peripheral and local forkhead box P3+ regulatory T cells in patients with non-small-cell lung cancer

Hasegawa

Suzuki

Yamaura

et al. 2014

Molecular and Clinical Oncology

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Abstract. Several types of immunosuppressive mechanisms in cancer patients have been reported to date. Regulatory T cells (Tregs), which express the master control transcription factor forkhead box P3 (FoxP3), are considered to play a major role in hampering antitumor immune response. However, the clinical significance of Tregs in patients with lung cancer has not been fully elucidated. The aim of this study was to investigate the clinical significance of Tregs in the peripheral blood and in resected cancer tissue specimens. We analyzed peripheral blood mononuclear cells (PBMCs) collected prior to surgery and resected specimens obtained from 67 patients with non-small-cell lung cancer (NSCLC). Peripheral Tregs (pTregs) were detected as CD4 + and FoxP3 + cells by flow cytometry. Immunohistochemical staining for CD4, CD8 and FoxP3 expression was also performed quantitatively by analyzing three randomly selected fields from central regions (cCD4, cCD8 and cFoxP3) and interstitial regions of the tumors (iCD4, iCD8 and iFoxP3). The associations between the expression frequencies in selected cells and clinicopathological parameters were statistically analyzed. The frequency of pTregs was found to be significantly higher in patients with pleural invasion (P=0.0049), vessel invasion (P=0.0009), lymphatic vessel invasion (P=0.0053) and recurrent disease (P=0.0112). Patients with T1 exhibited a significantly higher frequency of cCD4 (P=0.0199) and cCD8 (P=0.0058), although cFoxP3 expression was not significant (P= 0.0935). Patients with low levels of cFoxP3/iFoxP3 exhibited a significantly higher frequency of pTregs (P=0.0338) and patients with a high frequency of pTregs exhibited significantly poorer recurrence-free survival (P=0.0071). The multivariate analysis identified pTreg frequency as an independent prognostic factor (P=0.0458). Although the pathological analysis remains controversial, the frequency of pTregs in NSCLC patients may be a useful prognostic biomarker.

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“…Treg numbers and phenotype in tumor tissues using adjacent lungs as controls (2,33). Use of adjacent tumorfree tissue allows identification of tumor-specific, rather than tissue-specific, differences in Tregs and T cells, as discussed previously (34)(35)(36).…”

Section: Discussionmentioning

confidence: 99%

Human lung tumor FOXP+ Tregs upregulate four “Treg-locking” transcription factors

Akimova¹,

Zhang²,

Negorev³

et al. 2017

JCI Insight

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Foxp3+ Regulatory T Cells and Natural Killer Cells Distinctly Infiltrate Primary Tumors and Draining Lymph Nodes in Pulmonary Adenocarcinoma

Cited by 69 publications

References 28 publications

Tumor-Infiltrating Regulatory T Cells: Phenotype, Role, Mechanism of Expansion In Situ and Clinical Significance

Tumor-Infiltrating Regulatory T Cells: Phenotype, Role, Mechanism of Expansion In Situ and Clinical Significance

Prognostic value of peripheral and local forkhead box P3+ regulatory T cells in patients with non-small-cell lung cancer

Human lung tumor FOXP+ Tregs upregulate four “Treg-locking” transcription factors

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