Immunological Changes in Peripheral Blood Mononuclear Cells of Patients with Metastatic Renal Cell Carcinoma After Low Doses of Subcutaneous Immunotherapy with IFN-??-2b and IL-2

Moltó, Luis; Carballido, J; Manzano, L; Martínez-Martin, B.; Esquivel, F.; Chafer, J; Olivier, Carlos; Álvarez‐Mon, Melchor

doi:10.1097/00002371-199905000-00009

Cited by 15 publications

(8 citation statements)

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“…Therefore, instead of being related to 131 I treatment, it is possible that the decrease in CD4 þ T lymphocyte percentage observed in our patients during TSH-suppressive thyroxine treatment may reflect a response similar to that observed in patients with renal carcinoma after treatment with IFNa-2b and IL-2, consisting of an increase in the cytolytic activity of NK cells paralleled by a significant decrease in the percentage of CD4 þ lymphocytes, with no changes in the proliferative response to T-cell mitogenic signals (39).…”

Section: Discussionsupporting

confidence: 63%

The effects of thyroid hormones on circulating markers of cell-mediated immune response, as studied in patients with differentiated thyroid carcinoma before and during thyroxine withdrawal

Botella-Carretero

Prados²,

Manzano³

et al. 2005

eur j endocrinol

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Objective: To address the influence of thyroid hormones on circulating markers of cell-mediated immune response in an in vivo human model. Subjects and design: Twenty-two patients with stage I differentiated thyroid carcinoma were studied on the last day of thyroxine suppressive treatment, 4-7 days after withdrawal, and the day before whole body scanning. Three patients were excluded because of residual disease. Twenty euthyroid individuals served as controls. Serum thyrotrophin and thyroid hormones were measured by an immunometric assay, circulating cytokines by enzyme-linked immuno-sorbent assay and lymphoid populations by flow cytometry. Results: Thyroid function in patients changed from subclinical or mild hyperthyroidism at the first visit, to a situation of normal circulating levels of free thyroxine and triiodothyronine at the second, ending in a state of overt hypothyroidism. Thyroxine suppressive treatment in patients increased serum interleukin-18 concentrations (IL-18, mean^S.D., 280^122 vs 183^106 pg/ml, F ¼ 3.192, P ¼ 0.029), soluble interleukin-2 receptor levels (sIL-2R, 4368^1480 vs 2564^846 pg/ml, F ¼ 21.324, P , 0.001), and the percentage of natural killer (NK) cells in peripheral blood (15.9^8.6 vs 10.5^3.6%, F ¼ 4.977, P ¼ 0.004) compared with controls. After thyroxine withdrawal, serum levels of IL-18, sIL-2R and the percentage of NK cells decreased progressively. Conclusion: Our present results suggest that thyroid hormones modulate the cell-mediated immune response in humans. 153 223-230 European Journal of Endocrinology

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Section: Discussionsupporting

confidence: 63%

The effects of thyroid hormones on circulating markers of cell-mediated immune response, as studied in patients with differentiated thyroid carcinoma before and during thyroxine withdrawal

Botella-Carretero

Prados²,

Manzano³

et al. 2005

eur j endocrinol

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“…The IL‐2 treatment protocols used in immunological studies of HIV‐negative patients with cancer differ from those used in HIV+ patients. However, these studies demonstrated a generalized increase of lymphocytes, rather than a peculiar effect on a specific subpopulation (22–24). It is coinceivable that persistent immune activation and the concomitant immune dysregulation present in HIV disease make these patients unique in their response to IL‐2.…”

Section: Discussionmentioning

confidence: 94%

Different rates of CD4+ and CD8+ T‐cell proliferation in interleukin‐2–treated human immunodeficiency virus‐positive subjects

et al. 2001

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Background: Interleukin-2 (IL-2) has been used successfully to increase CD4 cell counts in patients who are human immunodeficiency virus (HIV) positive. The mechanisms involved in this phenomenon are unknown. We hypothesized that a differential proliferation rate of CD4؉ compared with CD8؉ lymphocytes could be related to the increase of CD4 counts and of CD4/CD8 ratios that occur in HIV؉ patients during IL-2 treatment. Methods: We enrolled in our study 14 HIV؉ patients treated with IL-2 or with highly active antiretroviral therapy (HAART) during a 96-week observation period. Using flow cytometry, we measured longitudinally the expression of the Ki67 antigen in peripheral blood CD4؉ and CD8؉ lymphocyte subsets. Results: Compared with HAART alone, IL-2 produced a rapid increase of Ki67؉ proliferating CD4 cells and a concomitant increase of the CD4/CD8 ratios, whereas the corresponding CD8 proliferation increased slightly. On the contrary, HAART alone was effective in suppressing equally both CD4 and CD8 proliferation. Conclusions: Our results suggest a selective activity of IL-2 on CD4 T-cell proliferation; on the contrary, CD8-specific proliferation is affected minimally during treatment. This information may offer the potential to plan correctly immune activating regimens. Cytometry (Comm. Clin. Cytometry) 46:233-237, 2001.

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“…Only a few studies have monitored NK cell cytotoxicity during immunotherapy in vivo, all of which only included patients with metastatic RCC [20][21][22][23][24]. They all showed a significant increase in NK cell cytotoxicity, except for one study in which the doses of rIL2 and rIFN-a were lower than those used in the present study [24]; only one study used rIL2 doses similar to those proposed by Buzio et al, but they were not combined with IFNa.…”

Section: Discussionmentioning

confidence: 80%

Natural killer cell cytotoxicity is enhanced by very low doses of rIL-2 and rIFN-α in patients with renal cell carcinoma

et al. 2008

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Very low doses of recombinant interleukin-2 (rIL-2) and interferon-alpha (rIFN-alpha) induce, in patients with advanced renal cell carcinoma (RCC) clinical response rate and median survival time comparable to other protocols, other than immunological response in terms of expansion of NK cells and cT lymphocytes. The aim of this pilot study was to verify whether very low dose immunotherapy can enhance NK cell cytotoxicity against tumoral target cells. Eight patients with advanced and 13 patients with localised disease received 4-week cycles of rIL-2 (total dose per week 7 MIU/m(2), s.c.) and rIFN-alpha (total dose per week 3.6 MUI/m(2), i.m.) according to the scheme proposed by Buzio et al. Neutrophils, monocytes, eosinophils, NK cells (CD56+bright, CD56+dimmer, CD3-CD56 +), NK-T cells (CD3+CD56+), Th-lymphocytes, cT-lymphocytes, HLA-DR+ and CD25+ lymphocytes and NK cell cytotoxicity were evaluated before and after cycle. The treatment led to the significant expansion of eosinophils (P < 0.001), NK cells (P < 0.001), CD56+bright (P < 0.001), CD56+dimmer (P < 0.001), Th-lymphocytes (P = 0.001), cT-lymphocytes (P = 0.014), HLA-DR+ (P = 0.007) and CD25+(P = 0.002) cells. Neutrophils significantly decreased (P = 0.001), whereas no significant effect was observed on monocytes (P = 0.22) or NK-T cells (P = 0.20). Patients with localised disease responded significantly better to treatment than metastatic patients in terms of the expansion of CD56+bright (P = 0.038), DR+ (P = 0.021), CD25+ (P = 0.006) and Th-lymphocytes (P = 0.014). The NK cell cytotoxicity was significantly increased by the immunotherapy in the whole population (P = 0.021) and similarly in the two groups of patients (P = 0.860); a reverse relation, even if not significant, was seen between the variation of NK-T cells and NK cells cytotoxicity (r = -0.39; P = 0.074).

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Immunological Changes in Peripheral Blood Mononuclear Cells of Patients with Metastatic Renal Cell Carcinoma After Low Doses of Subcutaneous Immunotherapy with IFN-??-2b and IL-2

Cited by 15 publications

References 0 publications

The effects of thyroid hormones on circulating markers of cell-mediated immune response, as studied in patients with differentiated thyroid carcinoma before and during thyroxine withdrawal

The effects of thyroid hormones on circulating markers of cell-mediated immune response, as studied in patients with differentiated thyroid carcinoma before and during thyroxine withdrawal

Different rates of CD4+ and CD8+ T‐cell proliferation in interleukin‐2–treated human immunodeficiency virus‐positive subjects

Natural killer cell cytotoxicity is enhanced by very low doses of rIL-2 and rIFN-α in patients with renal cell carcinoma

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