a The Royal Marsden NHS Foundation Trust , London , UK.
Expert Opin Investig Drugs. 2019 Aug;28(8):695-708. doi: 10.1080/13543784.2019.1649657. Epub 2019 Aug 6.
: Immunotherapy has revolutionized the treatment of cancer. Given this growing success, at the same time, there are significant limitations and unanswered questions concerning response rates, duration of therapy, why some patients respond and others do not, and if combining different immune-agents would overcome this lack of response, increase the chance of success and postpone acquired resistance. : The comprehension of how to properly modulate the immune pathways, the molecular and the immunological bases of the disease, will be fundamental to guide the development of therapeutic interventions and combinations that will be more suitable for treatment of cancer patients. In this review, we discuss the strategies of immunotherapy combinations in order to develop more effective immunotherapy programs, with a particular focus on melanoma and renal cancer patients, as well as the combination of immunotherapy and chemotherapy. : Given the complexity of immune activation, combinatorial approaches are needed, and due to the considerable variability in tumor biology across patients and tumor types, patient selection and biomarkers need to be further explored. In summary, combined therapies have shown promising success, but additional and continuous research to identify the safety, efficacy, optimal combination, dosage and timing are still required.
免疫疗法已经彻底改变了癌症的治疗方法。鉴于这种日益增长的成功，同时，对于反应率、治疗持续时间、为什么有些患者有反应而有些患者没有反应、以及如果联合使用不同的免疫制剂是否会克服这种反应缺乏、提高成功率和推迟获得性耐药性等问题，仍存在重大的局限性和未解决的问题。了解如何正确调节免疫途径、疾病的分子和免疫学基础，对于指导治疗干预和组合的发展至关重要，这些干预和组合将更适合癌症患者的治疗。在这篇综述中，我们讨论了免疫疗法组合的策略，以开发更有效的免疫疗法方案，特别关注黑色素瘤和肾癌患者，以及免疫疗法和化疗的联合应用。鉴于免疫激活的复杂性，需要采用组合方法，并且由于患者和肿瘤类型之间的肿瘤生物学存在相当大的可变性，因此需要进一步探索患者选择和生物标志物。总之，联合疗法已经显示出了有希望的成功，但仍需要更多和持续的研究来确定安全性、疗效、最佳组合、剂量和时间。
