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恶性胸膜间皮瘤免疫治疗的进展:从新兴策略到转化见解

Advances in Immunotherapy for Malignant Pleural Mesothelioma: From Emerging Strategies to Translational Insights.

作者信息

López-Castro Rafael, Fuentes-Martín Álvaro, Medina Del Valle Andrea, García Peña Tania, Soro García José, López González Leticia, Cilleruelo Ramos Ángel

机构信息

Faculty of Medicine, University of Valladolid, Spain.

Thoracic Surgery Department, Hospital Clínico Universitario de Valladolid, Spain.

出版信息

Open Respir Arch. 2024 Apr 5;6(3):100323. doi: 10.1016/j.opresp.2024.100323. eCollection 2024 Jul-Sep.

DOI:10.1016/j.opresp.2024.100323
PMID:38660145
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11041830/
Abstract

MPM stands as a rare malignancy necessitating improved therapeutic strategies due to its limited treatment choices and unfavorable prognosis. The advent of immune checkpoint inhibitors has heralded a paradigm shift in the therapeutic landscape of MPM, offering promising avenues across diverse clinical scenarios. In the context of advanced stages of the disease, Immune check-point inhibitors targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-as-sociated protein 4 (CTLA-4), have exhibited encouraging potential in clinical trials, particularly manifesting efficacy among patients exhibiting disease progression following chemotherapy regimens. Innovative combination regimens, exemplified by the concurrent administration of nivolumab and ipilimumab, have demonstrated marked improvement in survival and patient's benefits. A deeper comprehension of the intricate genetic underpinnings of MPM, encompassing key mutations such as cyclin-dependent kinase inhibitor 2A (CDKN2A), neurofibromin 2 (NF2), and BRCA1-associated protein 1 (BAP1) mutations, has elucidated novel avenues for targeted therapeutic interventions. This review accentuates the transformative capacity of immunotherapy in revolutionizing the therapeutic outlook for MPM, thereby potentially translating into augmented survival rates and offering glimpses of new approaches on the horizon. Despite the persisting challenges, the synergistic crossroads of interdisciplinary research and collaborative clinical endeavors portend a hopeful landscape for MPM treatment.

摘要

恶性胸膜间皮瘤(MPM)是一种罕见的恶性肿瘤,由于其治疗选择有限且预后不佳,需要改进治疗策略。免疫检查点抑制剂的出现预示着MPM治疗格局的范式转变,为各种临床情况提供了有前景的途径。在疾病晚期,靶向程序性细胞死亡蛋白1(PD-1)和细胞毒性T淋巴细胞相关蛋白4(CTLA-4)的免疫检查点抑制剂在临床试验中显示出令人鼓舞的潜力,尤其在化疗方案后出现疾病进展的患者中表现出疗效。以纳武单抗和伊匹单抗联合使用为例的创新联合方案,已显示出生存率和患者获益的显著改善。对MPM复杂基因基础的更深入理解,包括细胞周期蛋白依赖性激酶抑制剂2A(CDKN2A)、神经纤维瘤蛋白2(NF2)和BRCA1相关蛋白1(BAP1)突变等关键突变,为靶向治疗干预开辟了新途径。本综述强调了免疫疗法在彻底改变MPM治疗前景方面的变革能力,从而有可能提高生存率并展现新方法的前景。尽管挑战依然存在,但跨学科研究与临床协作努力的协同交汇为MPM治疗预示了充满希望的前景。

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