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间皮瘤的免疫治疗策略——肿瘤特异性新抗原在精准医学新时代的作用。

Immunotherapy strategies for mesothelioma - the role of tumor specific neoantigens in a new era of precision medicine.

机构信息

a Department of Medical Oncology , Sir Charles Gairdner Hospital , Nedlands , Australia.

b National Centre for Asbestos Related Disease , University of Western Australia , Nedlands , Australia.

出版信息

Expert Rev Respir Med. 2019 Feb;13(2):181-192. doi: 10.1080/17476348.2019.1563488. Epub 2018 Dec 30.

Abstract

Immunotherapy has long been considered a potential therapy for malignant mesothelioma and is currently being pursued as such. Some of the early phase clinical trials involving immunomodulators have demonstrated encouraging results and numerous clinical trials are underway to further investigate this treatment approach in various treatment settings and larger patient cohorts. Areas covered: This review summarizes the current and emerging clinical evidence for checkpoint blockade and other immunotherapeutic strategies in mesothelioma. The mesothelioma tumor immune microenvironment and mutational landscape are also discussed, including their impact on treatment strategies. We also provide an evaluation of the current evidence for neoantigen targeted personalized immunotherapy. Expert opinion: Immune checkpoint inhibitors work by unleashing the host immune response against probable neoantigens. Despite impressive activity in a small subset of patients and the potential for prolonged responses, most patients experience treatment failure. Neoantigen vaccines provide a potential complementary therapeutic strategy by increasing the immunogenic antigen load, which can lead to an increased tumor specific immune response. Further research is needed explore this treatment option in mesothelioma and technological advances are required to translate this concept into clinical practice.

摘要

免疫疗法长期以来一直被认为是恶性间皮瘤的一种潜在疗法,目前正在研究中。一些涉及免疫调节剂的早期临床试验已经取得了令人鼓舞的结果,许多临床试验正在进行中,以在各种治疗环境和更大的患者群体中进一步研究这种治疗方法。涵盖领域:本文综述了目前和新兴的临床证据,证明了检查点阻断和其他免疫治疗策略在间皮瘤中的作用。还讨论了间皮瘤肿瘤免疫微环境和突变景观,包括它们对治疗策略的影响。我们还评估了针对新抗原的个体化免疫治疗的现有证据。专家意见:免疫检查点抑制剂通过释放宿主对可能的新抗原的免疫反应起作用。尽管在一小部分患者中具有显著的活性和潜在的延长反应,大多数患者仍经历治疗失败。新抗原疫苗通过增加免疫原性抗原负荷提供了一种潜在的互补治疗策略,从而导致肿瘤特异性免疫反应增加。需要进一步研究探索这种治疗选择在间皮瘤和技术进步需要将这一概念转化为临床实践。

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