The Laboratory of Immunology, Department of Medicine and Moores Cancer Center, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0815, USA.
Ludwig Institute for Cancer Research, University of Lausanne, Agora Center, Rue du Bugnon 25A, 1005 Lausanne, Switzerland.
Cells. 2020 Jul 19;9(7):1727. doi: 10.3390/cells9071727.
Immune checkpoint inhibitors (ICPi) have shown their superiority over conventional therapies to treat some cancers. ICPi are effective against immunogenic tumors. However, patients with tumors poorly infiltrated with immune cells do not respond to ICPi. Combining ICPi with other anticancer therapies such as chemotherapy, radiation, or vaccines, which can stimulate the immune system and recruit antitumor T cells into the tumor bed, may be a relevant strategy to increase the proportion of responding patients. Such an approach still raises the following questions: What are the immunological features modulated by immunogenic therapies that can be critical to ensure not only immediate but also long-lasting tumor protection? How must the combined treatments be administered to the patients to harness their full potential while limiting adverse immunological events? Here, we address these points by reviewing how immunogenic anticancer therapies can provide novel therapeutic opportunities upon combination with ICPi. We discuss their ability to create a permissive tumor microenvironment through the generation of inflamed tumors and stimulation of memory T cells such as resident (T) and stem-cell like (T) cells. We eventually underscore the importance of sequence, dose, and duration of the combined anticancer therapies to design optimal and successful cancer immunotherapy strategies.
免疫检查点抑制剂 (ICPi) 在治疗某些癌症方面已经显示出优于传统疗法的优势。ICPi 对免疫原性肿瘤有效。然而，免疫细胞浸润不良的肿瘤患者对 ICPi 没有反应。将 ICPi 与其他抗癌疗法（如化疗、放疗或疫苗）联合使用，这些疗法可以刺激免疫系统并将抗肿瘤 T 细胞招募到肿瘤床中，可能是增加应答患者比例的相关策略。这种方法仍然提出了以下问题：免疫原性疗法调节的免疫特征对于确保不仅是即时的而且是持久的肿瘤保护至关重要的是什么？为了充分发挥联合治疗的潜力，同时限制免疫相关不良事件，应该如何给患者施用这些联合治疗？在这里，我们通过回顾免疫原性抗癌疗法如何在与 ICPi 联合使用时提供新的治疗机会来解决这些问题。我们讨论了它们通过产生炎症肿瘤和刺激记忆 T 细胞（如驻留（T）和干细胞样（T）细胞）来创造允许肿瘤生长的微环境的能力。我们最终强调了联合抗癌疗法的顺序、剂量和持续时间的重要性，以设计最佳和成功的癌症免疫治疗策略。
