Department of Immunology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China; Suzhou Blood Center, Suzhou 215006, China.
Department of Immunology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China; Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Cancer Treat Res Commun. 2021;28:100379. doi: 10.1016/j.ctarc.2021.100379. Epub 2021 Apr 23.
PD-1 immune checkpoint blockade and cytokine IL-33 have shown significant therapeutic effects in tumor immunotherapy. These therapies promote CD8 T cell activation, proliferation, and effector functions. However, there were few research about the combined therapy efficacy. In this study, we established B16-empty vector and B16-IL33 melanoma mouse models and treated with PD-1 monoclonal antibody. We reported that PD-1 blockade combined with cytokine IL-33 further inhibited tumor progression and prolonged the survival of tumor-bearing mice. Mechanistically, the combination therapy was found to further facilitate CD4 and CD8 T lymphocytes accumulation, and enhance the antitumor effects of CD4or CD8tumor-infiltrating lymphocytes by promoting type-1 immune response within the tumor microenvironment using flow cytometry and quantitative real time polymerase chain reaction. Thus, PD-1 blockade combined with IL-33 has application potential in tumor immunotherapy. Further, this study provides a new promising strategy and theoretical basis for tumor combination immunotherapy.
PD-1 免疫检查点阻断和细胞因子 IL-33 在肿瘤免疫治疗中显示出显著的治疗效果。这些治疗方法促进了 CD8 T 细胞的激活、增殖和效应功能。然而，关于联合治疗效果的研究较少。在这项研究中，我们建立了 B16-空载体和 B16-IL33 黑色素瘤小鼠模型，并使用 PD-1 单克隆抗体进行治疗。我们报告称，PD-1 阻断联合细胞因子 IL-33 进一步抑制了肿瘤进展，延长了荷瘤小鼠的生存时间。从机制上讲，通过流式细胞术和定量实时聚合酶链反应发现，联合治疗进一步促进了 CD4 和 CD8 T 淋巴细胞的积累，并通过促进肿瘤微环境中的 1 型免疫反应，增强了 CD4 或 CD8 肿瘤浸润淋巴细胞的抗肿瘤作用。因此，PD-1 阻断联合 IL-33 在肿瘤免疫治疗中有应用潜力。此外，本研究为肿瘤联合免疫治疗提供了一种新的有前途的策略和理论基础。
