Norton Duncan L, Haque Azizul
Department of Microbiology and Immunology, Charles Darby Children's Research Institute and Hollings Cancer Center, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA.
J Oncol. 2009;2009:142959. doi: 10.1155/2009/142959. Epub 2009 Nov 24.
Metastatic melanoma is one of the deadliest of skin cancers and is increasing in incidence. Since current treatment regimens are ineffective at controlling and/or curing the disease, novel approaches, such as immunotherapy, for treating this malignant disease are being explored. In this review, we discuss potential melanoma antigens (Ags) and their role in utilizing the HLA class II pathway to elicit tumor Ag-specific CD4+ T cell responses in order to effectively induce long-lasting CD8+ antitumor memory. We also discuss the role of endolysosomal cathepsins and Gamma-Interferon-inducible Lysosomal Thiol reductase (GILT) in Ag processing and presentation, and at enhancing CD4+ T cell recognition of melanoma cells. This review also summarizes our current knowledge on GILT and highlights a novel mechanism of GILT-mediated immune responses against melanoma cells. At the end, we propose a strategy employing GILT in the development of a potential whole cell vaccine for combating metastatic melanoma.
转移性黑色素瘤是最致命的皮肤癌之一，且发病率正在上升。由于目前的治疗方案在控制和/或治愈该疾病方面无效，因此正在探索诸如免疫疗法等治疗这种恶性疾病的新方法。在本综述中，我们讨论了潜在的黑色素瘤抗原（Ags）及其在利用HLA II类途径引发肿瘤抗原特异性CD4+ T细胞反应以有效诱导持久的CD8+抗肿瘤记忆方面的作用。我们还讨论了内溶酶体组织蛋白酶和γ-干扰素诱导的溶酶体硫醇还原酶（GILT）在抗原加工和呈递以及增强CD4+ T细胞对黑色素瘤细胞识别中的作用。本综述还总结了我们目前对GILT的认识，并强调了GILT介导的针对黑色素瘤细胞免疫反应的新机制。最后，我们提出了一种在开发用于对抗转移性黑色素瘤的潜在全细胞疫苗中应用GILT的策略。
