Mucosal Melanoma

Mucosal melanoma is considered an epidemic cancer as its worldwide incidence has increased 697% between 1950 and 2000, faster than that of any other cancer subtype; although, recent evidence suggests that this rise many have peaked. The American Cancer Society noe estimates thet the lifetime risk of developing melanoma is approximately 1 in 50 for Caucasians, 1 in 200 for African Americans. In the United States, invasive melanoma is the 6th most common cancer in men and the 7th in women; the lifetime probability of developing this tumor is 1 in 37 for males and 1 in 56 for females. An estimated 68,130 new cases of cutaneous melanoma were diagnosed in 2010, with 8,700 estimated deaths from this disease. While representing <7% of all skin malignancies, melanoma is the most lethal cutaneous malignancy and accounts for 75% of all deaths from skin tumors.

Melanoma tumors can demonstrate spontaneous immune-mediated regression. In addition, tumor-specific cytotoxic T-cells and antibodies may be found in the peripheral blood of patients with melanoma. Therefore, immunotheray is a potentially effective treatment strategy for individuals with the disease. One approach is the enhancement of anti-melanoma immune responses through the optimization of T-cell activation. The latter involves interactions between the T-cell receptor (TCR), the co-stimulatory receptor CD28, and the ligands CD80 and CD86.

T-cell inhibition is mediated by the inhibitory receptor, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), a molecule that shares 30% structural homology with CD28, and is expressed by activated T-cells and T-regulatory cells (Tregs). CLTA-4 binds CD80/CD86 with greather affinity than CD28 does, theraby inhibiting CD28-mediated T-cell activation and IL-2 production. CTLA-4 is critical in maintaining immune tolerance to self-antigens, but may also limit host responses to tumor antigens and the efficacy of vaccine therapy.