Rondon Lizbeth, Fu Roberto, Patel Manish R
Department of Medicine, Hennepin County Medical Center, Minneapolis, MN 55404, USA.
Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Cancers (Basel). 2023 May 27;15(11):2940. doi: 10.3390/cancers15112940.
Malignant pleural mesothelioma (MPM) is a malignancy associated with asbestos exposure and is typically categorized as an orphan disease. Recent developments in immunotherapy with anti-PD-1 and anti-CTLA-4 antibodies, specifically with agents nivolumab and ipilimumab, have demonstrated an improvement in overall survival over the previous standard chemotherapy leading to their FDA-approval as first-line therapy for unresectable disease. For quite some time, it has been known that these proteins are not the only ones that function as immune checkpoints in human biology, and the hypothesis that MPM is an immunogenic disease has led to an expanding number of studies investigating alternative checkpoint inhibitors and novel immunotherapy for this malignancy. Early trials are also supporting the notion that therapies that target biological molecules on T cells, cancer cells, or that trigger the antitumor activity of other immune cells may represent the future of MPM treatment. Moreover, mesothelin-targeted therapies are thriving in the field, with forthcoming results from multiple trials signaling an improvement in overall survival when combined with other immunotherapy agents. The following manuscript will review the current state of immune therapy for MPM, explore the knowledge gaps in the field, and discuss ongoing novel immunotherapeutic research in early clinical trials.
恶性胸膜间皮瘤（MPM）是一种与石棉暴露相关的恶性肿瘤，通常被归类为罕见病。抗程序性死亡蛋白1（PD-1）和抗细胞毒性T淋巴细胞相关蛋白4（CTLA-4）抗体免疫疗法的最新进展，特别是纳武单抗和伊匹单抗，已证明其总体生存率高于先前的标准化疗，从而获得美国食品药品监督管理局（FDA）批准作为不可切除疾病的一线治疗方法。很长一段时间以来，人们都知道这些蛋白质并非人类生物学中唯一发挥免疫检查点功能的蛋白质，并且MPM是一种免疫原性疾病这一假说促使越来越多的研究去探索针对这种恶性肿瘤的替代检查点抑制剂和新型免疫疗法。早期试验也支持这样一种观点，即针对T细胞、癌细胞上的生物分子或触发其他免疫细胞抗肿瘤活性的疗法可能代表着MPM治疗的未来。此外，针对间皮素的疗法在该领域蓬勃发展，多项试验即将得出的结果表明，与其他免疫治疗药物联合使用时可提高总体生存率。以下手稿将综述MPM免疫治疗的现状，探讨该领域的知识空白，并讨论早期临床试验中正在进行的新型免疫治疗研究。
