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Blockade of neutrophil recruitment to tumor sites based on sialic acid-modified nanoplatforms enhances the efficacy of checkpoint blockade immunotherapy.
- Source :
- Asian Journal of Pharmaceutical Sciences; Mar2023, Vol. 18 Issue 2, p1-12, 12p
- Publication Year :
- 2023
-
Abstract
- Checkpoint inhibitors are designed to rejuvenate depleted or suppressed T cells in the tumor microenvironment, relying on the immune system to control and kill tumors. However, accumulating evidence indicates that tumor-infiltrating neutrophils impede the proliferation and activation of T cells and determine the resistance to checkpoint blockade and chemotherapy. In this study, sialic acid ligand-modified colchicine derivative phospholipid complexes specifically targeted tumor-associated neutrophils in the peripheral blood, blocked neutrophil accumulation in tumors, and attenuated the inhibitory effect of infiltrating neutrophils on T cells. Neutrophil blocking therapy enhanced the immunotherapy effect of the PD-L1 antibody in S180 advanced tumors and 4T1 breast cancer. Our study found that PD-L1 antibody monotherapy increased the tumor infiltration of immunosuppressive neutrophils. Combination therapy with neutrophil blocking can greatly reduce tumor-infiltrating neutrophils and increase the proliferation of cytotoxic CD8 + T lymphocytes in the tumor. The combination therapy significantly improved the survival rate of mice with advanced S180 tumors and increased the sensitivity of immune checkpoint inhibitors to 4T1 cold tumors. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 18180876
- Volume :
- 18
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Asian Journal of Pharmaceutical Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 163444713
- Full Text :
- https://doi.org/10.1016/j.ajps.2023.100784