Terenziani Rita, Zoppi Silvia, Fumarola Claudia, Alfieri Roberta, Bonelli Mara
Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy.
Cancers (Basel). 2021 Jun 4;13(11):2793. doi: 10.3390/cancers13112793.
Malignant pleural mesothelioma (MPM) is a rare and aggressive malignant disease affecting the mesothelium, commonly associated to asbestos exposure. The current therapeutic actions, based on cisplatin/pemetrexed treatment, are limited due to the late stage at which most patients are diagnosed and to the intrinsic chemo-resistance of the tumor. Another relevant point is the absence of approved therapies in the second line setting following progression of MPM after chemotherapy. Considering the poor prognosis of the disease and the fact that the incidence of this tumor is expected to increase in the next decade, novel therapeutic approaches are urgently needed. In the last few years, several studies have investigated the efficacy and safety of immune-checkpoint inhibitors (ICIs) in the treatment of unresectable advanced MPM, and a number of trials with immunotherapeutic agents are ongoing in both first line and second line settings. In this review, we describe the most promising emerging immunotherapy treatments for MPM (ICIs, engineered T cells to express chimeric antigen receptors (CARs), dendritic cells (DCs) vaccines), focusing on the biological and immunological features of this tumor as well as on the issues surrounding clinical trial design.
恶性胸膜间皮瘤(MPM)是一种罕见且侵袭性强的恶性疾病,影响间皮,通常与接触石棉有关。目前基于顺铂/培美曲塞治疗的治疗措施有限,这是因为大多数患者确诊时已处于晚期,且肿瘤具有内在的化疗耐药性。另一个相关问题是,MPM化疗进展后的二线治疗中缺乏获批的疗法。鉴于该疾病预后较差,且预计未来十年这种肿瘤的发病率会上升,迫切需要新的治疗方法。在过去几年中,多项研究调查了免疫检查点抑制剂(ICI)治疗不可切除晚期MPM的疗效和安全性,并且一线和二线治疗中都有多项免疫治疗药物试验正在进行。在本综述中,我们描述了针对MPM最有前景的新兴免疫疗法(ICI、表达嵌合抗原受体(CAR)的工程化T细胞、树突状细胞(DC)疫苗),重点关注该肿瘤的生物学和免疫学特征以及围绕临床试验设计的问题。