Uchi Hiroshi, Stan Rodica, Turk Mary Jo, Engelhorn Manuel E, Rizzuto Gabrielle A, Goldberg Stacie M, Wolchok Jedd D, Houghton Alan N
Swim Across America Laboratory, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York, USA.
Adv Immunol. 2006;90:215-41. doi: 10.1016/S0065-2776(06)90006-6.
A relationship between melanoma and vitiligo, a skin disorder characterized by the loss of melanocytes, has been postulated for many decades. In some cases, vitiligo is almost certainly a manifestation of autoimmune-mediated destruction of melanocytes. Melanocytes and melanoma cells share melanocyte differentiation antigens. Based on a number of observations, de novo vitiligo developing in patients with melanoma has been regarded as a sign of good prognosis. The immune system tolerates or ignores differentiation antigens because these antigens are self-derived. Therefore, immune tolerance or ignorance must be overcome to prime naive T and B cells to induce cancer immunity and autoimmunity against melanocyte differentiation antigens. Mouse models of concurrent melanoma and autoimmune vitiligo have revealed strategies to overcome immune ignorance or tolerance to melanocyte differentiation antigens: immunization with self-antigens as altered self (e.g., orthologues or mutated versions), expression in viral vectors, passive immunization with antibodies or T cells, incorporating potent adjuvants into active immunization, and blockade or removal of a downregulatory mechanism. Extensive investigations into the mechanisms that lead to tumor immunity and autoimmunity elicited by certain differentiation antigens have further revealed a variety of distinct cellular and molecular requirements, which are redundant and alternative.
黑色素瘤与白癜风（一种以黑素细胞缺失为特征的皮肤疾病）之间的关系已被推测数十年。在某些情况下，白癜风几乎可以肯定是自身免疫介导的黑素细胞破坏的一种表现。黑素细胞和黑色素瘤细胞共享黑素细胞分化抗原。基于多项观察结果，黑色素瘤患者新发的白癜风被视为预后良好的标志。免疫系统耐受或忽略分化抗原，因为这些抗原是自身来源的。因此，必须克服免疫耐受或忽视，以启动幼稚T细胞和B细胞，诱导针对黑素细胞分化抗原的癌症免疫和自身免疫。黑色素瘤与自身免疫性白癜风并发的小鼠模型揭示了克服对黑素细胞分化抗原的免疫忽视或耐受的策略：用改变的自身抗原（如直系同源物或突变版本）进行免疫、在病毒载体中表达、用抗体或T细胞进行被动免疫、在主动免疫中加入强效佐剂，以及阻断或去除下调机制。对某些分化抗原引发肿瘤免疫和自身免疫的机制进行的广泛研究进一步揭示了各种不同的细胞和分子要求，这些要求是冗余的和可替代的。
