Institute of Cell Biology (Cancer Research), University Hospital Essen, 45147 Essen, Germany.
Int J Mol Sci. 2018 Dec 21;20(1):24. doi: 10.3390/ijms20010024.
In recent decades, technical advances in surgery and radiotherapy, as well as breakthroughs in the knowledge on cancer biology, have helped to substantially improve the standard of cancer care with respect to overall response rates, progression-free survival, and the quality of life of cancer patients. In this context, immunotherapy is thought to have revolutionized the standard of care for cancer patients in the long term. For example, immunotherapy approaches such as immune checkpoint blockade are currently increasingly being used in cancer treatment, either alone or in combination with chemotherapy or radiotherapy, and there is hope from the first clinical trials that the appropriate integration of immunotherapy into standard care will raise the success rates of cancer therapy to a new level. Nevertheless, successful cancer therapy remains a major challenge, particularly in tumors with either pronounced resistance to chemotherapy and radiation treatment, a high risk of normal tissue complications, or both, as in lung cancer. Chemotherapy, radiotherapy and immunotherapy have the capacity to evoke adverse effects in normal tissues when administered alone. However, therapy concepts are usually highly complex, and it is still not clear if combining immunotherapy with radio(chemo)therapy will increase the risk of normal tissue complications, in particular since normal tissue toxicity induced by chemotherapy and radiotherapy can involve immunologic processes. Unfortunately, no reliable biomarkers are available so far that are suited to predict the unique normal tissue sensitivity of a given patient to a given treatment. Consequently, clinical trials combining radiotherapy and immunotherapy are attracting major attention, not only regarding efficacy, but also with regard to safety. In the present review, we summarize the current knowledge of radiation-induced and immunotherapy-induced effects in tumor and normal tissue of the lung, and discuss the potential limitations of combined radio-immunotherapy in lung cancer with a focus on the suspected risk for enhanced acute and chronic normal tissue toxicity.
近几十年来，手术和放疗技术的进步，以及癌症生物学知识的突破，都有助于极大地提高癌症治疗的标准，包括总体反应率、无进展生存期和癌症患者的生活质量。在这种情况下，免疫疗法被认为从长远来看彻底改变了癌症患者的治疗标准。例如，免疫疗法方法，如免疫检查点阻断，目前越来越多地用于癌症治疗，无论是单独使用还是与化疗或放疗联合使用，并且从首次临床试验中可以看到，将免疫疗法适当地整合到标准治疗中，将把癌症治疗的成功率提升到一个新的水平。然而，成功的癌症治疗仍然是一个主要的挑战，特别是在那些对化疗和放疗有明显抵抗力、正常组织并发症风险高或两者兼有的肿瘤中，如肺癌。化疗、放疗和免疫疗法在单独使用时会对正常组织产生不良反应。然而，治疗方案通常非常复杂，目前仍不清楚将免疫疗法与放化疗相结合是否会增加正常组织并发症的风险，特别是因为化疗和放疗引起的正常组织毒性可能涉及免疫过程。不幸的是，目前还没有可靠的生物标志物可以预测特定患者对特定治疗的独特正常组织敏感性。因此，联合放疗和免疫疗法的临床试验引起了极大的关注，不仅涉及疗效，还涉及安全性。在本综述中，我们总结了目前关于肺肿瘤和正常组织中放射诱导和免疫治疗诱导效应的知识，并讨论了联合放化疗在肺癌中的潜在局限性，重点关注增强急性和慢性正常组织毒性的可疑风险。
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