Melanoma in Immunosuppressed Patients

doi:10.1016/j.mayocp.2012.04.018

Mayo Clinic Proceedings

Volume 87, Issue 10, October 2012, Pages 991-1003

https://doi.org/10.1016/j.mayocp.2012.04.018 Get rights and content

Abstract

The immunogenic characteristics of malignant melanoma are intriguing. To date, multiple studies exist regarding the immunogenicity of melanoma. In this article, we summarize data in the literature on the role of immunosuppression in melanoma and discuss several immunocompromised patient populations in detail. A comprehensive PubMed search was conducted with no date limitation. The following search terms were used: melanoma in combination with immunosuppression, immunocompromised, genetics, antigen processing, UV radiation, organ transplantation, organ transplant recipients, lymphoproliferative disease, lymphoma, CLL, NHL, radiation, and HIV/AIDS. Although no formal criteria were used for inclusion of studies, most pertinent studies on the topic were reviewed, with the exception of smaller case reports and case series. The included studies were generally large (≥1000 patients in organ transplant recipient studies; ≥500 patients in lymphoma studies), with a focus on institutional experiences, or population-based national or international epidemiologic studies. Melanoma-induced immunosuppression, the role of UV radiation in melanoma development, and the epidemiology, clinical course, and prognosis of melanoma in immunocompromised patients are highlighted. Organ transplant recipients, patients with lymphoproliferative disorders, patients with iatrogenic immunosuppression, and patients with human immunodeficiency virus infection/AIDS are also highlighted. Recommendations are proposed for the care and monitoring of immunosuppressed patients with melanoma. With better understanding of the molecular microenvironment and clinical course of melanoma in immunosuppressed patients, novel therapies could be developed and outcomes potentially affected in these patients.

Section snippets

Melanoma-Induced Immunosuppression

Within the biology of cancer, suppression of the normal immune response is pivotal in the ability of tumors to grow and metastasize. Cutaneous melanoma is an immunogenic tumor with the ability to spread via the lymphatic system while simultaneously evading and overcoming the body's tumor surveillance system.⁸ Melanoma-induced immunosuppression develops through numerous mechanisms, such as down-regulation of surface antigens, mutations within malignant cells, lack of costimulatory function,

The Melanoma Microenvironment

In normal physiologic responses, regulatory CD4⁺CD25⁺ T cells allow for development of peripheral immune tolerance; without these molecules, autoimmune reactions occur. In melanoma, these regulatory cells secrete immunosuppressive cytokines and suppress activation and proliferation of the antitumor immune response9, 10 (Boon et al 1997, Romero et al 1998, as cited in Viguier et al¹¹). These regulatory CD4⁺CD25⁺ T cells express FOXP3 and have been associated with failed clinical responses of

Melanoma and the Sun

The medical literature shows a consensus that extensive exposure to UV radiation is a risk factor for melanoma.¹⁹ Although the exact mechanism is not clear, experts have speculated that the combination of carcinogenic, inflammatory, and immunosuppressive elements of UV radiation contribute to this risk.¹⁹ The mechanism involves keratinocyte response to UV radiation, which induces melanocyte production of melanin.¹⁹ Ultraviolet radiation is a potent mutagen in keratinocyte DNA and has the

Melanoma in Solid Organ Transplant Recipients

Solid organ transplant recipients are a well-studied group of immunocompromised patients. Among these individuals, an increased incidence of both nonmelanoma skin cancer and melanoma has been reported extensively. Herein, we review the data on melanomas occurring after transplant. In addition, we elaborate on the clinical scenarios of patients with a history of melanoma before transplant and melanoma that resulted from transmission from the organ donor.²⁵

Melanoma in Lymphoproliferative Disease

Another group of immunocompromised patients are those with lymphoproliferative disorders. The incidence of not only melanoma but also lymphoma has increased in recent decades, making both these cancers particularly relevant—especially the overlap that exists between the 2 entities. Substantial literature chronicles melanoma in NHL and chronic lymphocytic leukemia (CLL) in particular; however, as in OTRs, much of the research thus far has focused on mechanisms of disease and incidence, with

Melanoma and Iatrogenic Immunosuppression

Within the larger spectrum of immunosuppression, iatrogenic causes are an important consideration, especially with the use of medications that suppress immune function. Whether these medications create a preferred environment for melanoma carcinogenesis or whether melanoma development is attributable to the direct effects of the medication is unclear.⁴¹ Of these medications, cyclosporine A, azathioprine, mycophenolate mofetil, corticosteroids, methotrexate, tacrolimus, 5-fluorouracil, and

Melanoma in Patients With Hiv Infection/Aids

Since the advent of highly active antiretroviral therapy (HAART), survival rates of patients infected with HIV have improved dramatically, which has altered the disease course.⁸⁹ HAART typically constitutes 3 or more medications that act through different HIV-attacking mechanisms. The number of AIDS-defining lesions and infections has decreased since the advent and frequent use of HAART in the mid-1990s. Still, the number has increased of chronic diseases that manifest because of adverse

Recommendations

Evidence-based decision making is limited in the care of immunosuppressed patients with melanoma. In general, treatment of immunocompromised patients should parallel the treatments of the immunocompetent population. Surgical excision typically is curative in early melanomas; therefore, vigilant screening and appropriate education are key for the immunocompromised population, in whom melanomas are not only more frequent but also have been shown to behave more aggressively.5, 94 In addition, a

Conclusion

Melanoma-induced immunosuppression and tumor evasion of normal immunologic reactions lead to the ability of melanoma to hide from the immune response. As melanoma incidence increases, populations of both OTRs and patients with lymphoproliferative disease grow, and patients with HIV infection live longer, there is also an increased need to learn about and understand the natural history, prognosis, and management of melanoma in the immunocompromised host. Although some literature about melanoma

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