Serum soluble interleukin–2 receptor concentrations as an independent prognostic marker in head and neck cancer

Tartour, Éric; Mosseri, Véronique; Jouffroy, Thomas; Deneux, Laurent; Jaulerry, C; Brunin, F.; Fridman, Wolf‐Herman; Rodriguez, J

doi:10.1016/s0140-6736(00)04420-2

Cited by 54 publications

(44 citation statements)

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“…This study confirms and extends previous reports about the prognostic value of serum sIL-2Ra in head and neck cancer [32,33] and reports, for the first time, the association between low MMP-9 serum concentrations prior to therapy and longer survival of head and neck cancer patients (Fig. 1a,b).…”

Section: Discussionsupporting

confidence: 92%

“…As reported previously [32,33], the sIL-2Ra assay measured both free sIL-2Ra and sIL-2Ra complexed to IL-2. A cut-off value of 70 pm corresponding to limits outside the 95-percentile ranges in healthy subjects was used to divide patients into two groups with high or low values.…”

Section: Assaysmentioning

confidence: 79%

“…in pM units or divided into two groups (high and low) based on a cut-off value of 70 pM corresponding to limits outside the 95-percentile ranges in healthy subjects as previously described [33]. As MMP-9 concentrations were distributed exponentially, they were expressed as geometric means and their associated confidence intervals in pg/ml or divided into two groups defined by a cut-off concentration of 95 ng/ml, corresponding to the median MMP-9 concentration.…”

Section: Discussionmentioning

confidence: 99%

“…We have reported previously a correlation between high serum sIL-2Ra levels at the time of diagnosis and a high risk of local or regional recurrence and poor survival in patients with head and neck squamous cell carcinoma (HNSCC) [32,33]. An overexpression of MMP-9 was observed in head and neck cancer tissues, with a frequency ranging from 20% to 52% of cases [34][35][36] and different groups found relationships between positive MMP-9 immunostaining or increased intratumoral MMP-9 activity in head and neck cancers and poor survival rates [35][36][37][38].…”

Section: Introductionmentioning

confidence: 99%

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Soluble interleukin-2 receptor and metalloproteinase-9 expression in head and neck cancer: prognostic value and analysis of their relationships

Agueznay

Badoual

Hans

et al. 2007

Clinical and Experimental Immunology

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SummaryIn a series of 84 head and neck patients, a statistically significant correlation was observed between high serum soluble interleukin (IL)-2 receptor alpha (sIL-2Ra) (P = 0·034) and metalloproteinase-9 (MMP-9) concentrations (P = 0·036) at diagnosis and a shorter survival of these patients. As MMP-9 has been shown to mediate cleavage of IL-2Ra (CD25) by preactivated T cells, we looked for a relationship between MMP-9 expression and soluble IL-2Ra serum concentrations in these cancer patients. We did not find any correlation between intratumoral expression of MMP-9 or serum MMP-9 concentrations and serum sIL-2Ra levels. These results led us to reassess the role of MMP-9 in the release of sIL-2Ra. Treatment of Kit225 leukaemic cells with recombinant MMP-9 slightly decreased membrane CD25 expression and was associated with an increased concentration of sIL-2Ra in the supernatants. However, using a selective inhibitor of MMP-9 we did not succeed in specifically inhibiting the release of sIL-2Ra by the Kit225 cell line or by phytohaemagglutinin (PHA)-activated peripheral blood mononuclear cells. In addition, in a preclinical mouse model, basal serum sIL-2Ra concentrations and sIL-2Ra production by activated cells were not altered in MMP-9-deficient mice compared to wild-type mice. Interestingly, a broad spectrum metalloproteinase inhibitor inhibited the release of sIL-2Ra by PHAactivated peripheral blood mononuclear cells, suggesting that in contrast with current views concerning the major role of MMP-9 in the cleavage of membrane IL-2Ra, other proteases are involved in the shedding of sIL-2Ra. MMP-9 and sIL-2Ra appear therefore as independent prognostic markers in head and neck cancers.

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Section: Discussionsupporting

confidence: 92%

Section: Assaysmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Soluble interleukin-2 receptor and metalloproteinase-9 expression in head and neck cancer: prognostic value and analysis of their relationships

Agueznay

Badoual

Hans

et al. 2007

Clinical and Experimental Immunology

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“…Third, specific subsets of Tregs, in particular those expressing activation markers such as CCR4, may exert more robust immunosuppressive functions, and hence be more closely associated with prognosis, than the entire population of Tregs [107]. Fourth, some oncogenic programs, such as those underlying (at least some instances of) lymphoma [108], head and neck cancer [109,110], gastric cancer [111] and colorectal carcinoma [112], involve a prominent pro-inflammatory component. In this setting, Treg-mediated immunosuppression may exert bona fide antitumor functions.…”

Section: Clinical Significance Of Intratumoral Tregsmentioning

confidence: 99%

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

Tanchot

Terme

Péré

et al. 2012

Cancer Microenvironment

112

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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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Denileukin Diftitox in Novel Cancer Therapy

Chen

Dang

2010

Emerging Cancer Therapy

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Serum soluble interleukin–2 receptor concentrations as an independent prognostic marker in head and neck cancer

Cited by 54 publications

References 4 publications

Soluble interleukin-2 receptor and metalloproteinase-9 expression in head and neck cancer: prognostic value and analysis of their relationships

Soluble interleukin-2 receptor and metalloproteinase-9 expression in head and neck cancer: prognostic value and analysis of their relationships

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

Denileukin Diftitox in Novel Cancer Therapy

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