The treatment of melanoma with an emphasis on immunotherapeutic strategies

Jack, Angela; Boyes, Christopher; Aydin, Nebil; Alam, Khorshed; Wallack, Marc K.

doi:10.1016/j.suronc.2006.05.003

Cited by 32 publications

(20 citation statements)

References 129 publications

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“…Several cytokines effectively enhance NKG2D-mediated immune response. IFN-a, which is frequently used in cancer therapies including therapies against melanoma (reviewed in Jack et al (2006)), upregulated NKG2D (Zhang et al, 2005a). The same group reported that NKG2D expression was enhanced in an NK cell line stably transfected with IL-15 .…”

Section: Perspectives Of Immunotherapy Exploiting Immune Cell Activatmentioning

confidence: 99%

NKG2D ligands in tumor immunity

2008

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The activating receptor NKG2D (natural-killer group 2, member D) and its ligands play an important role in the NK, cd þ and CD8 þ T-cell-mediated immune response to tumors. Ligands for NKG2D are rarely detectable on the surface of healthy cells and tissues, but are frequently expressed by tumor cell lines and in tumor tissues. It is evident that the expression levels of these ligands on target cells have to be tightly regulated to allow immune cell activation against tumors, but at the same time avoid destruction of healthy tissues. Importantly, it was recently discovered that another safeguard mechanism controlling activation via the receptor NKG2D exists. It was shown that NKG2D signaling is coupled to the IL-15 receptor pathway in a cell-specific manner suggesting that priming of NKG2D-mediated activation depends on the cellular microenvironment and the distinct cellular context. This review will provide a broad overview of our up-to-date knowledge of the NKG2D receptor and its ligands in the context of tumor immunology. Strategies to amplify NKG2D-mediated antitumor responses and counteract tumor immune escape mechanisms will be discussed.

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Section: Perspectives Of Immunotherapy Exploiting Immune Cell Activatmentioning

confidence: 99%

NKG2D ligands in tumor immunity

2008

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“…In addition, DC are easily cultured and differentiated in vitro, and pulsed with peptides, proteins or lysates from tumor cells. However, DC-based vaccines produced inconsistent results in clinical trials although increasing T cell immune activation up to 80-90% [52].…”

Section: V)mentioning

confidence: 99%

New Perspectives for Melanoma Immunotherapy: Role of IL-12

Cocco

Pistoia

Airoldi

2009

CMM

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Metastatic melanoma is a poor prognosis skin cancer. Since conventional treatments including surgery and chemotherapy often fail, novel therapeutic strategies are needed. In particular, identification of melanoma associated antigen has fostered the progress of both active (vaccines) and adoptive immunotherapy. Some promising results have been obtained, but most melanoma patients are not yet cured possibly because of different immune-escape mechanisms operated by tumor cells. Several studies have addressed the use of interleukin (IL)-12 for melanoma therapy due to its immunoregulatory function and anti-tumor activity mediated by stimulation of T and NK effector cells. Unfortunately, IL-12 has shown considerable toxicity. We [1] have recently demonstrated that IL-12 exerts a direct anti-tumor activity on murine B16 melanoma cells expressing a functional IL-12 receptor (R). In our model low levels of endogenous IL-12 reduced proliferation, increased apoptosis, and defective microvessel formation of tumor cells. This review summarizes information about melanoma immunotherapy and highlights a novel mechanism of IL-12-mediated anti-tumor activity based upon the direct effect of the cytokine on IL-12R(+) tumor cells. In this view, new therapeutic approaches may be planned including: i) pre-screening of melanoma patients for IL-12Rbeta2 expression to identify potential responders, ii) administration of small and less frequent doses of IL-12 to avoid toxicity and iii) targeting of IL-12 to IL-12R(+) tumor cells, such as local administration in patients with skin tumors or injection of IL-12 fused to an antibody specific to tumor cells.

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“…In the United States, CMM is an emerging problem as the incidence has increased more than that of any other cancer over the past two decades. More specifically, in 2005 the American Cancer Society recorded approximately 59,580 new cases and over 7,910 new deaths [3,4].…”

Section: Introductionmentioning

confidence: 99%

Genetic factors in metastatic progression of cutaneous melanoma: the future role of circulating melanoma cells in prognosis and management

Ireland

Millward

Pearce

et al. 2011

Clin Exp Metastasis

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The greatest potential for improvement of outcome for patients with Cutaneous Malignant Melanoma lies in the prevention of systemic metastasis. Despite extensive investigation, current prognostic indicators either alone or in combination, although related to melanoma progression, are not sufficient to accurately predict the pattern of progression and outcome for any individual patient. Metastasis related death has been recorded in patients initially diagnosed with early stage tumour as well as in patients many years after initial tumour removal. The trouble finding a predictable pattern in the puzzle of melanoma progression may be linked to the fact that most of the material studied for prognosis is either, cutaneous primaries or metastatic deposits, rather than the melanoma cells in the circulatory system which are responsible for disease progression. In this review article we discuss the potential use of circulating tumour cell (CTC) detection and quantification for identifying patients at risk of metastatic deposits. We also discuss current therapies for the treatment of metastatic melanoma and analyse how CTCs may be used to evaluate the effectiveness of current therapies and to pinpoint patients who require further treatment.

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The treatment of melanoma with an emphasis on immunotherapeutic strategies

Cited by 32 publications

References 129 publications

NKG2D ligands in tumor immunity

NKG2D ligands in tumor immunity

New Perspectives for Melanoma Immunotherapy: Role of IL-12

Genetic factors in metastatic progression of cutaneous melanoma: the future role of circulating melanoma cells in prognosis and management

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