Weiner David M, Durgin Joseph S, Wysocka Maria, Rook Alain H
Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
J Am Acad Dermatol. 2021 Mar;84(3):597-604. doi: 10.1016/j.jaad.2020.12.026. Epub 2020 Dec 22.
In the past few decades, immunotherapy has emerged as an effective therapeutic option for patients with cutaneous T cell lymphoma (CTCL). CTCL is characterized by progressive impairment of multiple arms of the immune system. Immunotherapy targets these deficits to stimulate a more robust antitumor response, thereby both clearing the malignant T cells and repairing the immune dysfunction. By potentiating rather than suppressing the immune system, immunotherapy can result in longer treatment responses than alternatives such as chemotherapy. In recent years, advances in our understanding of the pathogenesis of CTCL have led to the development of several new agents with promising efficacy profiles. The second article in this continuing medical education series describes the current immunotherapeutic options for treatment of CTCL, with a focus on how they interact with the immune system and their treatment outcomes in case studies and clinical trials. We will discuss established CTCL immunotherapies, such as interferons, photopheresis, and retinoids; emerging therapies, such as interleukin-12 and Toll-like receptor agonists; and new approaches to targeting tumor antigens and checkpoint molecules, such as mogamulizumab, anti-programmed cell death protein 1, anti-CD47, and chimeric antigen receptor T cell therapy. We also describe the principles of multimodality immunotherapy and the use of total skin electron beam therapy in such regimens.
在过去几十年中,免疫疗法已成为皮肤T细胞淋巴瘤(CTCL)患者的一种有效治疗选择。CTCL的特征是免疫系统的多个分支逐渐受损。免疫疗法针对这些缺陷来刺激更强有力的抗肿瘤反应,从而清除恶性T细胞并修复免疫功能障碍。通过增强而非抑制免疫系统,免疫疗法可能比化疗等其他治疗方法产生更长时间的治疗反应。近年来,我们对CTCL发病机制认识的进展导致了几种具有良好疗效的新药物的开发。这个继续医学教育系列的第二篇文章描述了目前用于治疗CTCL的免疫治疗选择,重点是它们如何与免疫系统相互作用以及在病例研究和临床试验中的治疗结果。我们将讨论已确立的CTCL免疫疗法,如干扰素、光分离置换法和维甲酸;新兴疗法,如白细胞介素-12和Toll样受体激动剂;以及靶向肿瘤抗原和检查点分子的新方法,如莫加莫拉单抗、抗程序性细胞死亡蛋白1、抗CD47和嵌合抗原受体T细胞疗法。我们还描述了多模式免疫疗法的原则以及在这些治疗方案中使用全身皮肤电子束疗法的情况。