期刊
CANCER NANOTECHNOLOGY
卷 13, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12645-022-00116-z
关键词
CXCL9; 10; 11; Infiltration; T cell; PD1; Cancer
资金
- Cangzhou Science and Technology Research and Development Program [204106108]
In this study, delivery of CXCL9/10/11 plasmids by nanoparticles was shown to enhance T cell infiltration in tumors, and the combination with anti-PD1 antibody exhibited the best anti-tumor effects.
Background Immune checkpoint blockade (ICB)-based cancer immunotherapy presents promising efficacy in cancer treatment. However, only a small portion of patients show responsiveness to the treatment, which is partially caused by limited tumor infiltration of T cells. Chemokines CXCL9, CXCL10 and CXCL11 bind to their receptor CXCR3 to regulate T cell invasion. Methods We delivered plasmids encoding CXCL9, CXCL10 and CXCL11 to tumor cells and tumor tissues using nanoparticles and investigated their effect on T cell invasion and infiltration. In addition, we applied these nanoparticles together with anti-PD-1 antibody, which is known to activate T cells and restore immune function against tumor cells. The anti-tumor effects were evaluated. Results Delivering plasmids encoding CXCL9, CXCL10 and CXCL11 by nanoparticles resulted in expression of these chemokines in both LLC cells and tumors. Expressing CXCL9, CXCL10 and CXCL11 promoted the infiltration of T cells in vitro and in vivo, as well as decreased the tumor size. Nanoparticles together with anti-PD-1 displayed the best anti-tumor effects. Conclusions Delivery of CXCL9/10/11 plasmids by nanoparticles promoted T cell infiltration in tumors and synergizes with the activity of anti-PD1 antibody.
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