PD-1 blockade combined with IL-33 enhances the antitumor immune response in a type-1 lymphocyte-mediated manner

Abstract

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 CD4⁺or CD8⁺tumor-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.

Keywords: IL-33; Immune checkpoint blockade; Melanoma; PD-1; Tumor immunotherapy.