Immunotherapy for melanoma

The immunogenicity of melanoma and the identification of melanoma-associated antigens is the basis for immunotherapy. This review will discuss the current status of melanoma immunotherapy with a focus on non-specific cytokines and highly specific vaccines, including peptides, viruses, dendritic cells, and whole cell vaccines. The passive transfer of melanoma-specific monoclonal antibodies and T-cells will also be reviewed. The problem of tumor escape and the association of immunotherapy to autoimmunity will be discussed. The use of immunotherapy in combination with other therapeutic agents and genetic profiling to predict responses suggests that immunotherapy will continue to play a role in the treatment of melanoma.     

Screening for melanoma

This article describes major screening studies of the past two decades, discusses the evidence-based screening recommendations, highlights the need to screen high-risk and previously unscreened populations, and concludes with suggestions for risk assessment and physician-nurse training in the skin cancer examination.     

Screening for melanoma

Dialogues in Dermatology, a monthly audio program from the American Academy of Dermatology, contains discussions between dermatologists on timely topics. Commentaries from Dialogues Editor-in-Chief Warren R. Heymann, MD, are provided after each discussion as a topic summary and are provided here as a special service to readers of the Journal of the American Academy of Dermatology.     

Vaccines for melanoma

Melanoma vaccines are now an accepted but still experimental treatment for patients who have been rendered clinically free of disease by surgical resection but are at high risk of recurrence and in selected patients with advanced but still limited disease. In general, there seems to be a correlation between the ability of melanoma vaccines to stimulate antimelanoma cellular or antibody immune responses and improved clinical outcome. Accordingly, a number of strategies are now being pursued to improve the clinical effectiveness of this first generation of vaccines by improving their ability to stimulate antimelanoma immunity. To establish the true effectiveness of vaccines in the treatment of malignant melanoma, several large, prospectively randomized phase III studies are currently being conducted.     

黑素瘤发病的危险因素

黑素瘤是一种高度恶性肿瘤,多发生于皮肤,在皮肤恶性肿瘤中死亡率最高.近年来在世界范围内黑素瘤的发生正在逐年增高,其发病的危险因素成为研究的热点.随着分子遗传学的发展,尤其是黑素瘤高危易感基因CDKN2A和CDK4的发现,使得遗传危险因素在黑素瘤发病中的地位日益重要.而环境因素（紫外线照射）、表型的高危性（皮肤颜色、发色及色素痣）、人群社会经济地位、职业以及药物等在黑素瘤的发病中也有着重要作用.同时基因检测及临床长期随访也是降低黑素瘤发病危险性的因素.     

恶性黑素瘤的免疫治疗研究进展

恶性黑素瘤是一种恶性度高、转移早、进展快、预后差及死亡率高等特点的皮肤肿瘤,对传统治疗方法如放疗和化疗均不敏感且疗效差,目前缺少较为有效的治疗方案.恶性黑素瘤为免疫源性较高的肿瘤,因此,恶性黑素瘤的免疫治疗研究已成为其个体化综合治疗的重要组成部分及研究热点.肿瘤免疫治疗是刺激人体自身免疫系统来抵抗癌症的治疗方法,具有特异性强、疗效持久和不良反应小等优点.目前通过免疫调节性单克隆抗体治疗、细胞因子治疗、疫苗治疗和过继性T细胞治疗等多种治疗方式单独或联合应用于恶性黑素瘤的治疗,显著改善了恶性黑素瘤患者的预后,为研发恶性黑素瘤新治疗方案提供了思路.     

黑素瘤发病的危险因素

黑素瘤是一种高度恶性肿瘤,多发生于皮肤,在皮肤恶性肿瘤中死亡率最高.近年来在世界范围内黑素瘤的发生正在逐年增高,其发病的危险因素成为研究的热点.随着分子遗传学的发展,尤其是黑素瘤高危易感基因CDKN2A和CDK4的发现,使得遗传危险因素在黑素瘤发病中的地位日益重要.而环境因素(紫外线照射)、表型的高危性(皮肤颜色、发色及色素痣)、人群社会经济地位、职业以及药物等在黑素瘤的发病中也有着重要作用.同时基因检测及临床长期随访也是降低黑素瘤发病危险性的因素.

Abstract：

Melanoma is a highly malignant tumor of melanocytes and predominantly involves the skin.It is the most deadly form of skin cancers.The incidence of melanoma has been steadily increasing in recent decades,and risk factors associated with melanoma development have attracted more and more attention from researchers in this field.Ultraviolet radiation (UVR) exposure,in the form of intermittent heavy exposure and severe sunburns in childhood,is believed to be the most important environmental contribution to melanoma risk.Genetic determinants also modulate melanoma risk,probably to a greater extent than environmental exposure.Two high-penetrance melanoma susceptibility genes,CDKN2A and CDK4,have so far been identified.Phenotypic markers of high-risk include skin color,hair color,pigmented nevi,etc.Other risk factors include socioeconomic status,occupations and ingestion of therapeutic drugs.Genetic detection and long-term clinical follow-up may reduce the risk for melanoma.     

Serum markers for melanoma

Tumor markers in the serum of cancer patients have an important role in clinical diagnosis and in prognosis, and also in the monitoring of the patients' disease and response to therapy over time. The serum markers currently available for melanoma have only limited clinical use. Those most widely used in clinical applications are S100-beta, melanoma inhibitory activity, and lactate dehydrogenase; there are close correlations between the serum concentrations of these and tumor load. Regular determination of S100-beta and MIA levels during follow-up can therefore be used for early detection of a tumor relapse in melanoma patients, increased serum concentrations of these marker proteins being indicative of tumor growth. Patients with distant metastases from melanoma who present with elevated serum levels of S100-beta, MIA, or LDH have poorer overall survival than do patients whose serum concentrations are within normal ranges. These three markers can also be used to monitor the course of disease and therapy outcome in patients with distant metastases. Since there are no marker proteins for melanoma that are not dependent on tumor load, it is not currently possible to forecast the survival of patients who are tumor free after surgery. Serum markers are also not suitable for screening or for the diagnosis of primary melanomas.     

Prognostic factors for melanoma

The current melanoma staging system, as defined by the American Joint Committee on Cancer (AJCC), is the standard by which melanoma prognosis is determined. This article focuses on the components of the AJCC melanoma staging system regarding patient prognosis. In addition, this article summarizes the other commonly researched clinical and histologic melanoma prognostic factors and reviews the recent advancements in genetic biomarkers associated with prognosis.     

恶性黑素瘤的免疫治疗进展

恶性黑素瘤是一种恶性度高、侵袭性强的难治性皮肤肿瘤,对传统治疗方法如放疗和化疗不敏感,疗效不令人满意.免疫学方法治疗恶性黑素瘤已成为研究热点.免疫学方法是一种用免疫细胞或免疫制剂来调节机体的免疫状态,从而治疗疾病的方法,具有特异性强、不良反应小等优点.可以通过多种治疗方式如细胞因子治疗、过继细胞治疗和特异性免疫治疗等单独或联合应用于恶性黑素瘤的治疗,具有较高的有效率并延长了患者的生存期,为治疗恶性黑素瘤带来了希望.     

Immunotherapy for advanced melanoma

Immunotherapy for melanoma has undergone significant change since the first attempts to treat patients with high dose IL-2. Herein, strategies to boost patient antitumor immunity through vaccination, treatment with agents that augment host immunity, and adoptive cell transfer will be discussed. The first two strategies have yielded only limited clinical success, but adoptive cell transfer therapy, particularly following a lymphodepleting, preconditioning regimen has resulted in objective response rates approaching 50%. For a number of reasons, lymphodepletion appears to be critical for maintenance of circulating antitumor T cells following adoptive cell transfer. Balancing antitumor efficacy, autoimmunity, and reconstitution of a functioning immune system remain challenging and potentially life-threatening issues.     

Interferon-alpha therapy for melanoma

Although surgery may be curative in early malignant melanoma, its effect on survival lessens with each succeeding stage of the disease. A wide variety of immunological strategies have therefore been used to improve the prognosis of patients with malignant melanoma, but adjuvant therapy with interferon (IFN)-alpha is the only treatment to show a therapeutic benefit in randomized controlled studies. The current data indicates that where IFN-alpha is used at low dose, its main effect is on disease-free survival, whereas high-dose regimens may improve overall survival as well. This paper will review the published data on IFN-alpha therapy in patients with intermediate and high-risk melanoma and explore future avenues for managing patients with this difficult disease.     

Radiation therapy for cutaneous melanoma

Radiation therapy is used infrequently for cutaneous melanoma, despite research suggesting benefit in certain clinical scenarios. This review presents data forming the highest level of evidence supporting the use of radiation therapy. Retrospective and prospective studies demonstrate radiation therapy for primary tumors is associated with high control rates. Two randomized trials have found improvements in regional control with adjuvant radiotherapy to regional lymphatics. Retrospective and prospective studies demonstrate radiation therapy is associated with palliative response and metastatic tumor control. Optimal care of melanoma patients involves radiation therapy; awareness of this is incumbent of clinicians caring for patients with this disease.