Reduction of circulating regulatory T cells by intravenous high-dose interferon alfa-2b treatment in melanoma patients

2012 ◽  
Vol 29 (7) ◽  
pp. 801-805 ◽  
Author(s):  
Nicola Mozzillo ◽  
Paolo Ascierto
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Interferon Alfa ◽  
High Dose ◽  
Melanoma Patients ◽  
High Dose Interferon

Regulatory T cells and other lymphocyte subpopulations in patients with melanoma developing interferon-induced thyroiditis during high-dose interferon-α2b treatment

2013 ◽  
Vol 78 (4) ◽  
pp. 621-628 ◽  
Author(s):  
Berta Soldevila ◽  
Núria Alonso ◽  
Maria J. Martínez-Arconada ◽  
Maria L. Granada ◽  
Aram Boada ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Lymphocyte Subpopulations ◽  
High Dose ◽  
High Dose Interferon ◽  
Interferon Α2b

Dose-Dependent Treatment Benefit in High-Risk Melanoma Patients Receiving Adjuvant High-Dose Interferon Alfa-2b

2005 ◽  
Vol 20 (3) ◽  
pp. 280-289 ◽  
Author(s):  
Michael Fluck ◽  
Darab Kamanabrou ◽  
Andrea Lippold ◽  
Martina Reitz ◽  
Jens Atzpodien
Keyword(s):  
High Risk ◽  
Interferon Alfa ◽  
High Dose ◽  
Treatment Benefit ◽  
High Risk Melanoma ◽  
Risk Melanoma ◽  
Melanoma Patients ◽  
Dose Dependent ◽  
High Dose Interferon

High-Dose Interferon Alfa-2b Significantly Prolongs Relapse-Free and Overall Survival Compared With the GM2-KLH/QS-21 Vaccine in Patients With Resected Stage IIB-III Melanoma: Results of Intergroup Trial E1694/S9512/C509801

2001 ◽  
Vol 19 (9) ◽  
pp. 2370-2380 ◽  
Author(s):  
John M. Kirkwood ◽  
Joseph G. Ibrahim ◽  
Jeffrey A. Sosman ◽  
Vernon K. Sondak ◽  
Sanjiv S. Agarwala ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Interferon Alfa ◽  
High Dose ◽  
Treatment Benefit ◽  
Significant Treatment ◽  
Melanoma Patients ◽  
Intergroup Trial ◽  
Resected Stage ◽  
High Dose Interferon

PURPOSE: Vaccine alternatives to high-dose interferon alfa-2b therapy (HDI), the current standard adjuvant therapy for high-risk melanoma, are of interest because of toxicity associated with HDI. The GM2 ganglioside is a well-defined melanoma antigen, and anti-GM2 antibodies have been associated with improved prognosis. We conducted a prospective, randomized, intergroup trial to evaluate the efficacy of HDI for 1 year versus vaccination with GM2 conjugated to keyhole limpet hemocyanin and administered with QS-21 (GMK) for 96 weeks (weekly × 4 then every 12 weeks × 8). PATIENTS AND METHODS: Eligible patients had resected stage IIB/III melanoma. Patients were stratified by sex and number of positive nodes. Primary end points were relapse-free survival (RFS) and overall survival (OS). RESULTS: Eight hundred eighty patients were randomized (440 per treatment group); 774 patients were eligible for efficacy analysis. The trial was closed after interim analysis indicated inferiority of GMK compared with HDI. For eligible patients, HDI provided a statistically significant RFS benefit (hazard ratio [HR] = 1.47, P = .0015) and OS benefit (HR = 1.52, P = .009) for GMK versus HDI. Similar benefit was observed in the intent-to-treat analysis (RFS HR = 1.49; OS HR = 1.38). HDI was associated with a treatment benefit in all subsets of patients with zero to ≥ four positive nodes, but the greatest benefit was observed in the node-negative subset (RFS HR = 2.07; OS HR = 2.71 [eligible population]). Antibody responses to GM2 (ie, titers ≥ 1:80) at days 29, 85, 365, and 720 were associated with a trend toward improved RFS and OS (P2 = .068 at day 29). CONCLUSION: This trial demonstrated a significant treatment benefit of HDI versus GMK in terms of RFS and OS in melanoma patients at high risk of recurrence.

Duration of High-Dose Interferon Alfa-2b Regimen for Resected High-Risk Melanoma

2009 ◽  
Vol 27 (25) ◽  
pp. e82-e83 ◽  
Author(s):  
Sanjiv S. Agarwala ◽  
Robert J. Gray ◽  
Michael K.K. Wong
Keyword(s):  
High Risk ◽  
Interferon Alfa ◽  
High Dose ◽  
High Risk Melanoma ◽  
Risk Melanoma ◽  
High Dose Interferon

Adjuvant PD-1 inhibitor versus high-dose interferon α-2b for Chinese patients with cutaneous and acral melanoma: A retrospective cohort analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21516-e21516
Author(s):  
Jiuhong Wang ◽  
Jingjing Li ◽  
Xing Liu ◽  
Xizhi Wen ◽  
Dandan Li ◽  
...  
Keyword(s):  
Cutaneous Melanoma ◽  
Chinese Patients ◽  
Interferon Α ◽  
High Dose ◽  
Free Survival ◽  
Acral Melanoma ◽  
Treatment Groups ◽  
Melanoma Patients ◽  
Metastatic Sites ◽  
High Dose Interferon

e21516 Background: The clinical efficacy of PD-1 inhibitors as an adjuvant treatment for Asian melanoma patients has not yet been determined. Methods: Thus, this single-centre, retrospective study analysed the clinical data of 90 Chinese patients with completely resected, stage III cutaneous or acral melanoma who received either adjuvant PD-1 inhibitor or high-dose interferon α-2b (HDI). Propensity score matching (PSM) was used to control baseline differences between the two treatment groups. The primary end point was recurrence-free survival (RFS), and the secondary end points included distance metastasis-free survival (DMFS) and incidence of first distant metastatic sites. Results: Anti-PD-1 treatment resulted in significantly longer RFS (18-month RFS, 53.3% versus 26.7%; 95% CI, 0.097-0.975; P < 0.05) and DMFS (18-month DMFS, 70.9% versus 46.1%; 95% CI, 0.13-0.945; P < 0.05) than HDI in cutaneous melanoma patients. However, adjuvant anti-PD-1 treatment had no advantage over HDI in acral melanoma patients (18-month RFS, 30.0% versus 35.9%; P > 0.05; 18-month DMFS, 36.5% versus 63.6%; P > 0.05). The incidence of lung metastasis at first in the anti-PD-1 group was found to be significantly lower (12.5% versus 48.5%; P < 0.05) in cutaneous melanoma patients than in acral melanoma patients, but no difference in metastatic sites were observed between the two treatment groups among acral melanoma patients. The incidence of treatment-related AEs was similar between the two treatment groups. Conclusions: In conclusion, adjuvant anti-PD-1 treatment was well tolerated and yielded a significantly better prognosis than HDI in Chinese patients with stage IIIB/C cutaneous melanoma, but a significant difference was not observed in those with acral melanoma.

scholarly journals Induction of Regulatory T Cells by High-Dose gp96 Suppresses Murine Liver Immune Hyperactivation

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e68997 ◽  
Author(s):  
Xinghui Li ◽  
Zhen Liu ◽  
Xiaoli Yan ◽  
Xiaojun Zhang ◽  
Yang Li ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
High Dose ◽  
Murine Liver

Lymphocyte Subpopulations and Interleukin Levels in High-Risk Melanoma Patients Treated With High-Dose Interferon A-2B

2002 ◽  
Vol 25 (6) ◽  
pp. 591-596 ◽  
Author(s):  
Helen Gogas ◽  
George Paterakis ◽  
Konstantina Frangia ◽  
Dimitrios Bafaloukos ◽  
Dimitrios Pectasides ◽  
...  
Keyword(s):  
High Risk ◽  
Lymphocyte Subpopulations ◽  
High Dose ◽  
High Risk Melanoma ◽  
Risk Melanoma ◽  
Melanoma Patients ◽  
High Dose Interferon

Abstract P288: Systemic Administration of an Angiotensin Type-2 Receptor Agonist Decreases Renal Regulatory T Cells

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Ellen E Gillis ◽  
Jennifer C Sullivan
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Critical Role ◽  
High Dose ◽  
Ang Ii ◽  
Osmotic Minipump ◽  
Angiotensin Type 2 Receptor ◽  
Angiotensin Type

There is increasing evidence supporting a critical role of the immune system in the development of hypertension. Our lab has previously reported sex differences in the renal T cell profile in both Spontaneously Hypertensive Rats (SHR) and Angiotensin II (Ang II) models of hypertension, with females having more anti-inflammatory regulatory T cells (Tregs) than males. Ang II has a well-defined role in the activation of pro-inflammatory T cells in hypertension via the angiotensin type-1 receptor (AT1R). Less is known about the role of the angiotensin type-2 receptor (AT2R) in the regulation of immune cells, although the AT2R has been shown to be cardioprotective and AT2R expression is greater in females than males. Based on the potential anti-hypertensive role of AT2Rs, we hypothesized that administration of an AT2R agonist, Compound 21 (C21), would increase renal Tregs, and this increase would be greater in females due to greater AT2R expression. Male and female SHR (10 weeks of age, n=3-4) were implanted with telemetry units for continuous monitoring of mean arterial pressure (MAP). Following 10 days of recovery, baseline MAP was recorded for 5 days. Rats were then divided into the following treatment groups: surgical controls, low dose C21 (150 ng/kg/min, sc by osmotic minipump), high dose C21 (300 ng/kg/min, sc by osmotic minipump). Kidneys were harvested after 2 weeks of treatment and flow cytometry was performed on whole kidney homogenates. MAP was not altered by C21 treatment in males (137±4 vs 134±4 vs 134±4 mmHg; n.s.) or females (128±2 vs 136±5 vs 134±4 mmHg; n.s.). Interestingly, despite having no effect on MAP, there was a significant decrease in renal CD3 + CD4 + FoxP3 + Tregs in females following both low and high doses of C21 (data expressed as % CD3 + CD4 + cells: 6±0.6 vs 3±0.6 vs 3.5±1.3 %, respectively; p=0.02). Tregs decrease in males following the high dose of C21 only (data expressed as % CD3 + CD4 + cells: 3.3±0.3 vs 3.3±0.5 vs 1.7±0.7 %, respectively; p=0.05). Total CD3 + T cells, CD3 + CD4 + T cells, and Th17 cells were not altered by C21 treatment. In conclusion, AT2R activation suppresses renal Tregs, and females are more sensitive than males. These data suggest a novel role for AT2R regulation in the kidney in hypertension.

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