RESUMO
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.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Interleucina-33/uso terapêutico , Melanoma Experimental/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias Cutâneas/tratamento farmacológico , Animais , Anticorpos Monoclonais Humanizados/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular Tumoral , Sinergismo Farmacológico , Feminino , Inibidores de Checkpoint Imunológico/farmacologia , Imunoterapia , Interleucina-33/farmacologia , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Camundongos Transgênicos , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologiaRESUMO
Interleukin-33 (IL-33) is a cytokine with pleiotropic functions in various diseases; however, its role in the antitumor immune response is still unclear. We found the expression of IL-33/ST2 in nonsmall cell lung tumor microenvironment. Furthermore, we found that IL-33 promoted effector functions of CD8+ T cells that play a critical role in antitumor immune response. In addition, we found that IL-33 enhanced tumor vaccine effector functions in mice. Altogether, these findings suggest that IL-33, through facilitates CD8+ T cells in microenvironment to provide a profound effect in antitumor immunotherapy.