University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
Semin Immunopathol. 2011 Jul;33(4):385-91. doi: 10.1007/s00281-011-0247-y. Epub 2011 Jan 31.
Since the pivotal cooperative group trials in the 1980's-90's,, high-dose interferon (HDI) has been the standard of adjuvant therapy. Despite multiple other trials evaluating potential new therapies in melanoma, HDI remains the only FDA-approved therapy for stage IIB and III melanoma. Initial reports from the more recent phase III international trials of modifications of the original HDI regimen linked the appearance of autoimmunity with improved outcomes of disease. Trials of high-dose interleukin-2, many years earlier, reported anecdotal observations that were consistent with the hypothesis that autoimmunity and clinical benefit of immunotherapies of melanoma are linked with one another. The only prospectively conducted study examining the appearance of clinical and laboratory evidence of autoimmunity during HDI therapy was published by Gogas and colleagues, demonstrating statistically significant impact on relapse-free survival and overall survival. Retrospectively conducted studies of different intermediate dosage regimens of interferon (IFN) have not fully confirmed the linkage of serological evidence of autoimmunity and improved survival outcomes. With the emergence of new immunotherapies in treatment of melanoma, this review highlights the importance of autoimmunity for future applications in melanoma and reviews significant differences of past studies evaluating the appearance of autoimmunity during IFN therapy in high-risk melanoma.
自 20 世纪 80 年代至 90 年代的关键合作组试验以来，高剂量干扰素（HDI）一直是辅助治疗的标准。尽管有多项其他试验评估了黑色素瘤的潜在新疗法，但 HDI 仍然是唯一获得 FDA 批准用于 IIB 期和 III 期黑色素瘤的疗法。最近对原始 HDI 方案进行修改的 III 期国际试验的初步报告表明，自身免疫与疾病转归的改善有关。多年前高剂量白细胞介素-2 的试验报告了一些与假设一致的轶事观察结果，即自身免疫与黑色素瘤免疫治疗的临床获益有关。唯一一项前瞻性研究检查了在 HDI 治疗期间出现临床和实验室自身免疫证据的情况，该研究由 Gogas 及其同事发表，表明对无复发生存率和总生存率有统计学意义的影响。对不同中间剂量干扰素（IFN）方案的回顾性研究并未完全证实血清学自身免疫证据与改善的生存结果之间的联系。随着新的免疫疗法在黑色素瘤治疗中的出现，这篇综述强调了自身免疫在黑色素瘤未来应用中的重要性，并回顾了过去评估 IFN 治疗期间自身免疫出现的研究的显著差异，这些研究评估了 IFN 治疗期间自身免疫出现的情况。
