Rafique Imran, Kirkwood John M, Tarhini Ahmad A
University of Pittsburgh Medical Center, Pittsburgh, PA.
University of Pittsburgh Medical Center, Pittsburgh, PA; University of Pittsburgh Cancer Institute, Pittsburgh, PA.
Semin Oncol. 2015 Jun;42(3):436-47. doi: 10.1053/j.seminoncol.2015.02.012. Epub 2015 Feb 14.
The quality of the host immune response in patients with advanced melanoma is compromised with a bias towards Th2-type polarization and a tumor microenvironment that facilitates disease progression. Overcoming tumor-induced immune suppression through strategies that build upon the immunomodulatory qualities and clinical activity of interferon-α as demonstrated in the melanoma adjuvant setting is a major clinical need. The recent advances in the field of immune checkpoint modulation and the unprecedented clinical activity in advanced melanoma opens the door on novel combinations that may overcome tumor tolerogenic mechanisms that are known to suppress the potent anti-tumor impact of interferon (IFN)-α. Promising preliminary data suggest that such combinations may move the clinical management of advanced melanoma into the next level, beyond what is currently seen with immune checkpoint blockers alone.
晚期黑色素瘤患者的宿主免疫反应质量受损，倾向于Th2型极化，且肿瘤微环境促进疾病进展。在黑色素瘤辅助治疗中所展现的，基于干扰素-α的免疫调节特性和临床活性的策略来克服肿瘤诱导的免疫抑制，是一项重大的临床需求。免疫检查点调节领域的最新进展以及晚期黑色素瘤前所未有的临床活性，为可能克服已知抑制干扰素（IFN）-α强效抗肿瘤作用的肿瘤耐受机制的新型联合疗法打开了大门。有前景的初步数据表明，此类联合疗法可能将晚期黑色素瘤的临床管理提升到一个新水平，超越目前单独使用免疫检查点阻断剂的效果。
