Elevated plasma soluble interleukin 2 receptor level correlates with defective natural killer and CD8+ T-cells in myelodysplastic syndromes

Yokose, Norio; Ogata, Kíyoyuki; Ito, Toshiharu; An, Emi; Tamura, Hideto; Dan, Kazuo; Hamaguchi, Hiroyuki; Sakamaki, Hisashi; Onozawa, Y; Nomura, Takeo

doi:10.1016/0145-2126(94)90060-4

Cited by 20 publications

(9 citation statements)

References 23 publications

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“…In 1984, Kerndrup et al, noticed that the decreased NK activity seen in patients with MDS was caused by a decreased number of circulating NK cells [5]. In 1994, Yokose et al, correlated the decreased absolute number of CD3−CD16+ and CD3−CD56+ cells, in patients that had a high risk of MDS, with an increased plasmatic level of sIL-2R [11]. The authors hypothesized that plasma sIL-2R is produced by malignant MDS cells in the bone marrow and could impair IL-2 stimulated growth of NK cells.…”

Section: Tumor Escape From Nk Cell Surveillance: Role Of Nk Cellsmentioning

confidence: 99%

Hematological Malignancies Escape from NK Cell Innate Immune Surveillance: Mechanisms and Therapeutic Implications

Farnault

Sanchez

Baier

et al. 2012

Clinical and Developmental Immunology

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Hematological malignancies treatment improved over the last years resulting in increased achievement of complete or partial remission, but unfortunately high relapse rates are still observed. Therefore, sustainment of long-term remission is crucial. Immune system has a key role in tumor surveillance. Natural killer (NK) cells, at the frontier of innate and adaptive immune system, have a central role in tumor cells surveillance as demonstrated in the setting of allogenic stem cell transplantation. Nevertheless, tumor cells develop various mechanisms to escape from NK cells innate immune pressure. Abnormal NK cytolytic functions have been described in nearly all hematological malignancies. We present here various mechanisms involved in the escape of hematological malignancies from NK cells surveillance: NK cells quantitative deficiency and NK cell qualitative deficiency by increased inhibition signaling or decreased activating stimuli. A challenge of immunotherapy is to restore an efficient antitumor response. A combination of classical therapy plus immune modulation strategies will soon become a standard of care for hematological malignancies.

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Section: Tumor Escape From Nk Cell Surveillance: Role Of Nk Cellsmentioning

confidence: 99%

Hematological Malignancies Escape from NK Cell Innate Immune Surveillance: Mechanisms and Therapeutic Implications

Farnault

Sanchez

Baier

et al. 2012

Clinical and Developmental Immunology

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“…One limitation of using sIL2R level as a prognostic parameter is that the levels can be elevated in other conditions such as asthma [12] autoimmune diseases [13,14] or other malignancies [15,16]. Clinicians should carefully assess possible underlying diseases when interpreting the result of sIL2R levels in patients with lymphoma.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of serum soluble interleukin-2 receptor level in patients with diffuse large B cell lymphoma, treated with CHOP- or RCHOP-based therapy

Oki¹,

Kato²,

Matsuo

et al. 2008

Leukemia & Lymphoma

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The emergence of rituximab has changed the clinical outcome of patients with B-cell lymphoma, which necessitates reassessment of previously determined prognostic factors. Thus, we evaluated the prognostic significance of serum soluble interleukin-2 receptor (sIL2R) levels in patients with diffuse large B cell lymphoma (DLBCL), treated with CHOP (n = 108) or RCHOP (n = 94). Serum sIL2R level ranged from 316 to 23 800 U/mL (median 1064 U/mL) and levels were generally higher in higher IPI risk group. Multivariate analyses revealed that sIL2R > or =1000 U/mL was associated with shorter progression free survival [hazard ratio (HR) = 2.52, p = 0.011] and overall survival (HR = 2.34, p = 0.037) independent of IPI risk group or rituximab use. Further subgroup analyses revealed that the impact of sIL2R was most apparent in patients with IPI low risk, both in CHOP alone and RCHOP group. Our study confirmed the prognostic value of sIL2R in patients with DLBCL with low International Prognostic Index (IPI) risk, also in the era of rituximab.

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“…(2) In addition to the finding that the plasma sIL-2R level is elevated in high-risk MDS, the plasma sIL-2R level was suggested to correlate positively with the total mass of MDS cells (Yokose et al, 1994); thus the plasma sIL-2R level may correlate with disease progression in MDS. In this study we examined the relationship between the plasma sIL-2R level and the clinical outcome in MDS patients.…”

Section: Discussionmentioning

confidence: 99%

“…(1) sIL-2R is thought to bind to and neutralize endogenous IL-2 in some disease states, and it thus may derange the immunologic function of hosts (Symons et al, 1988;Rubin et al, 1986). In addition, we showed previously that there was a negative correlation between the plasma sIL-2R level and the absolute number of CD8 T cells and natural killer (NK) cells in MDS (Yokose et al, 1994). T and NK cells are thought to play a role in eliminating malignant cells and infections and in regulating haemopoiesis (Hamaguchi et al, 1990;Hogan & Basten, 1988;Herberman, 1992;Haller et al, 1977;Garcia-Penarrubia et al, 1989;Pistoia et al, 1985;Robertson & Ritz, 1990); thus an abnormality of these cells may influence the disease progression itself, the defence mechanisms against infections and the peripheral blood cell count.…”

Section: Discussionmentioning

confidence: 99%

Plasma soluble interleukin‐2 receptor level in patients with primary myelodysplastic syndromes: a relationship with disease subtype and clinical outcome

Ogata

Yokose

et al. 1996

Br J Haematol

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To assess the hypothesis that the plasma soluble interleukin-2 receptor (sIL-2R) level may have predictive value for morbidity/mortality in patients with myelodysplastic syndromes (MDS), we determined in plasma sIL-2R level of 80 MDS patients and examined their subsequent clinical course. Compared with low-risk MDS (refractory anaemia (RA) and RA with ringed sideroblasts) patients and normal subjects, the plasma sIL-2R level was significantly elevated in high-risk MDS (three other MDS subtypes and acute leukaemia following MDS) patients (high-risk MDS versus low-risk MDS, P < 0.01; high-risk MDS versus normal subjects, P < 0.01). 14/40 low-risk MDS patients developed at least one of the following during the follow-up period: erythrocyte transfusion dependence, infections requiring hospitalization, disease progression or MDS-related death. The plasma sIL-2R level was higher in these eventful subjects than in event-free low-risk subjects (P < 0.0001), and all of 10 low-risk subjects with a plasma sIL-2R level > 540 U/ml experience at least one event. By logistic regression analysis of various parameters in these 40 low-risk subjects, the plasma sIL-2R level was identified as the strongest independent parameter for predicting eventful subjects (P < 0.0047). The plasma sIL-2R level did not show a predictive value in high-risk MDS. This study revealed that the plasma sIL-2R level is significantly elevated in high-risk MDS and suggested that the plasma sIL-2R level is a valuable predictive factors for the clinical outcome in low-risk MDS.

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Elevated plasma soluble interleukin 2 receptor level correlates with defective natural killer and CD8+ T-cells in myelodysplastic syndromes

Cited by 20 publications

References 23 publications

Hematological Malignancies Escape from NK Cell Innate Immune Surveillance: Mechanisms and Therapeutic Implications

Hematological Malignancies Escape from NK Cell Innate Immune Surveillance: Mechanisms and Therapeutic Implications

Prognostic value of serum soluble interleukin-2 receptor level in patients with diffuse large B cell lymphoma, treated with CHOP- or RCHOP-based therapy

Plasma soluble interleukin‐2 receptor level in patients with primary myelodysplastic syndromes: a relationship with disease subtype and clinical outcome

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