In the last 10 years a deeper understanding of the immune landscape of cancers, including immune-evasion processes, has allowed the development of a new class of agents. The re-activation of host anti-tumor immune response, offers the potential for long-term survival benefit in a portion of patients with thoracic malignancies. The advent of programmed death-1 (PD-1) / programmed death ligand-1 (PD-L1) immune-checkpoint inhibitors (ICI), both as single agents and in combination with chemotherapy, and more recently combination of ICI, anti-PD1 and anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody, have led to breakthrough therapeutic advances for patients with advanced non-small cell lung cancer (NSCLC) and to a lesser extent, patients with small cell lung cancer (SCLC). Encouraging activity has recently emerged in pre-treated patients with thymic carcinoma. Conversely in malignant pleural mesothelioma, pivotal positive signs of activity have not been fully confirmed in randomized trials. The additive effects of chemoradiation and immunotherapy suggested intriguing potential for therapeutic synergy with combination strategies. This has led to the introduction of ICI consolidation therapy in stage III NSCLC creating a platform for future therapeutic developments in earlier stage disease. Despite the definitive clinical benefit observed with ICI, primary and acquired resistance represent well-known biological phenomena, which may significantly impact the therapeutic efficacy of these agents. The development of innovative strategies to overcome ICI resistance, standardization of new patterns of ICI progression, identification of predictive biomarkers of response, optimal treatment duration, and characterization of ICI efficacy in special populations, represent crucial issues to be adequately addressed, with the aim of improving the therapeutic benefit of ICI in patients with thoracic malignancies. In the current paper, an international panel of experts in the field of thoracic malignancies discussed these topics, evaluating currently available scientific evidence, with the final aim of providing clinical recommendations, which may guide oncologists in their current practice, and elucidate future treatment strategies and research priorities.

中文翻译：

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胸部恶性肿瘤中的免疫检查点抑制剂：IASLC 专家小组对现有证据的审查和建议

在过去的 10 年里，对癌症免疫环境的更深入了解，包括免疫逃避过程，已经允许开发出一类新的药剂。宿主抗肿瘤免疫反应的重新激活，为部分胸部恶性肿瘤患者提供了长期生存获益的潜力。程序性死亡-1 (PD-1) / 程序性死亡配体-1 (PD-L1) 免疫检查点抑制剂 (ICI) 的出现，无论是作为单一药物还是与化疗联合，以及最近的 ICI、抗- PD1 和抗细胞毒性 T 淋巴细胞抗原 4 (CTLA-4) 抗体为晚期非小细胞肺癌 (NSCLC) 患者和小细胞肺癌 (SCLC) 患者带来了突破性的治疗进展）。最近在预先治疗的胸腺癌患者中出现了令人鼓舞的活动。相反，在恶性胸膜间皮瘤中，关键的阳性活动体征尚未在随机试验中得到充分证实。放化疗和免疫疗法的累加效应表明联合策略具有治疗协同作用的有趣潜力。这导致在 III 期 NSCLC 中引入 ICI 巩固治疗，为早期疾病的未来治疗发展创造了平台。尽管 ICI 观察到了明确的临床益处，但原发性和获得性耐药代表了众所周知的生物学现象，这可能会显着影响这些药物的治疗效果。开发克服 ICI 阻力的创新策略，标准化 ICI 进展的新模式，识别反应的预测性生物标志物、最佳治疗持续时间和 ICI 在特殊人群中的疗效表征，代表了需要充分解决的关键问题，目的是提高 ICI 对胸部恶性肿瘤患者的治疗益处。在当前的论文中，胸部恶性肿瘤领域的一个国际专家小组讨论了这些主题，评估了当前可用的科学证据，最终目的是提供临床建议，指导肿瘤学家目前的实践，并阐明未来的治疗策略和研究重点。旨在提高 ICI 对胸部恶性肿瘤患者的治疗效果。在当前的论文中，胸部恶性肿瘤领域的一个国际专家小组讨论了这些主题，评估了当前可用的科学证据，最终目的是提供临床建议，指导肿瘤学家目前的实践，并阐明未来的治疗策略和研究重点。旨在提高 ICI 对胸部恶性肿瘤患者的治疗效果。在当前的论文中，胸部恶性肿瘤领域的一个国际专家小组讨论了这些主题，评估了当前可用的科学证据，最终目的是提供临床建议，指导肿瘤学家目前的实践，并阐明未来的治疗策略和研究重点。