Durable Complete Responses With High-Dose Bolus Interleukin-2 in Patients With Metastatic Melanoma Who Have Experienced Progression After Biochemotherapy

Tarhini, Ahmad A.; Kirkwood, John M.; Gooding, William E.; Cai, Chao; Agarwala, Sanjiv S.

doi:10.1200/jco.2006.10.2822

Cited by 72 publications

(47 citation statements)

References 21 publications

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“…High-dose bolus IL-2 therapy and adoptive cell transfer of T cells activated ex vivo with this cytokine have been shown to induce significant clinical responses in advanced melanoma patients (13,23,24). However, development of immune dysfunction affecting T-cell responsiveness to g chain cytokines as IL-2 may hamper the efficacy of such therapeutic approaches.…”

Section: Resultsmentioning

confidence: 99%

“…In the instance of melanoma, the characterization of patients for T-cell responsiveness to g chain cytokines as IL-2 would be relevant to identify subsets that may benefit from clinical use of this cytokine (13). To this end, in this study, we evaluated proliferation and STAT activation upon stimulation with IL-2 in T-lymphocyte subsets from melanoma patients at different stages of disease.…”

mentioning

confidence: 99%

“…A significant implication of these results is that the ability of cancer patients' T cells to respond to cytokines of the g chain family (upon ex vivo activation) is a key requisite for antigen-independent expansion and differentiation of T-cell populations to be used in adoptive immunotherapy settings (11). Retained T-cell responsiveness to cytokines as IL-2, IL-15, and IL-21 may be essential even for the generation of T-cell effectors in vivo, in the context of active immunotherapy, as well as for the efficacy of therapy based on the administration of high dose IL-2 to patients with advanced melanoma (13). This possibility is also in agreement with experimental models, indicating that tumor reactive IL-2Ra -/-CD8 + T cells fail to control established tumors (14) and that IL-15 and IL-21 have cooperative effects in CD8 + -mediated tumor regression (12).…”

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confidence: 99%

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Impaired STAT Phosphorylation in T Cells from Melanoma Patients in Response to IL-2: Association with Clinical Stage

Mortarini¹,

Vegetti²,

Molla³

et al. 2009

Clinical Cancer Research

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Purpose: To assess the extent of signal transducer and activator of transcription (STAT) activation in response to interleukin 2 (IL-2) in melanoma patients' T cells, along with clinical stage of tumor progression. Experimental Design:T lymphocytes from peripheral blood of healthy donors and of American Joint Committee on Cancer stage I to IV melanoma patients, as well as from metastatic lymph nodes of patients, were evaluated for responsiveness to IL-2. CFSE assays and single-cell phospho-STAT^specific flow cytometry screening were used. Results. Tcells from advanced melanoma patients, in comparison with healthy donors, showed reduced proliferation to IL-2 and IL-15, but not to anti-CD3 monoclonal antibody. Impaired response occurred in CCR7 + and CCR7 -T-cell subsets, but not in CD3 -CD8 + natural killer (NK) cells, and was not explained by induction of apoptosis, increased cytokine consumption, or altered IL-2R subunit expression in patients' T lymphocytes. By phospho-specific flow cytometry, defective STAT1and STAT5 activation in response to IL-2 was found mainly inT lymphocytes from peripheral blood and/or tumor site of American Joint Committee on Cancer stage III and IV patients, compared with stage I and II patients and to donors, and in melanoma antigen-specific Tcells isolated from metastatic lymph nodes. At tumor site, impaired STATactivation inTcells did not correlate with frequency of CD4 + CD25 + Foxp3 + T cells. Serum from advanced melanoma patients inhibited IL-2^dependent STATactivation in donors' Tcells and a neutralizing monoclonal antibody to transforming growth factor h1counteracted such inhibition. Conclusions: These results provide evidence for development of impaired STAT signaling in response to IL-2, along with clinical evolution of the disease, in melanoma patients' Tcells.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Impaired STAT Phosphorylation in T Cells from Melanoma Patients in Response to IL-2: Association with Clinical Stage

Mortarini¹,

Vegetti²,

Molla³

et al. 2009

Clinical Cancer Research

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“…However, due to its toxicity and difficulty with administration, IL-2 therapy could only be used in a small percentage of selected patients [30]. In recent years, the interest in BRAF inhibitors and immunotherapy is increasing due to the evidence of efficacy on the overall survival rate in patients with metastatic melanoma.…”

Section: Discussionmentioning

confidence: 99%

Metastatic melanoma of the gallbladder: report of two cases and a review of the literature

et al. 2015

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Melanoma is one of the most aggressive and highly metastatic cancers. The most common sites of distant metastases are soft tissues, lung, liver, skin and brain, whereas only few patients develop gastrointestinal metastases. Metastatic involvement of the gallbladder is rare and more often part of a widespread disease than a solitary lesion. The "gold-standard" treatment of metastatic melanoma of the gallbladder remains unclear. We report two cases of patients with past history of cutaneous melanoma who developed visceral metastases. The first patient was asymptomatic and had a widespread disease with metastatic involvement of both the spleen and the gallbladder. The second patient had an isolated metastasis of the gallbladder and complained of upper abdominal pain. The chosen treatment was open cholecystectomy (and splenectomy) in the first case and laparoscopic cholecystectomy in the second. A review of the literature is provided.

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“…It was first administered for malignant melanoma and renal cell carcinoma with approximately 7% long lasting reported complete response rate. However, this treatment modality, although effective has significant adverse events resulting from cytokine release and activation of immune response and needs to be administered in specialized centers supervised by trained medical professionals [48,49].…”

Section: Interleukinmentioning

confidence: 99%

Emerging Role of Interleukins in Cancer Treatment

Razavi¹,

Allen²

2014

Immunome Res

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Durable Complete Responses With High-Dose Bolus Interleukin-2 in Patients With Metastatic Melanoma Who Have Experienced Progression After Biochemotherapy

Abstract: HDB IL-2 is active therapy for patients who experience progression on BCT. This observation has implications regarding the importance of dose-intensity for IL-2 therapy.

Cited by 72 publications

References 21 publications

Impaired STAT Phosphorylation in T Cells from Melanoma Patients in Response to IL-2: Association with Clinical Stage

Impaired STAT Phosphorylation in T Cells from Melanoma Patients in Response to IL-2: Association with Clinical Stage

Metastatic melanoma of the gallbladder: report of two cases and a review of the literature

Emerging Role of Interleukins in Cancer Treatment

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