Journal
SCIENCE ADVANCES
Volume 6, Issue 20, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aaz9240
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Funding
- National Key Research and Development Program of China [2017YFA0205402]
- Science Fund for Distinguished Young Scholars of Jiangsu Province, China [BK20170028]
- China National Science Foundation [81573377, 81872817]
- Double First-Class University Project of China Pharmaceutical University [CPU2018GY07]
- Changjiang Scholar Program
- University of Nebraska Medical Center
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Anti-programmed cell death 1 ligand 1 (PD-L1) therapy is extraordinarily effective in select patients with cancer. However, insufficient lymphocytic infiltration, weak T cell-induced inflammation, and immunosuppressive cell accumulation in the tumor microenvironment (TME) may greatly diminish the efficacy. Here, we report development of the FX@HP nanocomplex composed of fluorinated polymerized CXCR4 antagonism (FX) and paclitaxel-loaded human serum albumin (HP) for pulmonary delivery of anti-PD-L1 small interfering RNA (siPD-L1) to treat orthotopic lung tumors. FX@HP induced T cell infiltration, increased expression of calreticulin on tumor cells, and reduced the myeloid-derived suppressor cells/regulatory T cells in the TME, thereby acting synergistically with siPD-L1 for effective immunotherapy. Our work suggests that the CXCR4-inhibiting nanocomplex decreases tumor fibrosis, facilitates T cell infiltration and relieves immunosuppression to modulate the immune process to improve the objective response rate of anti-PD-L1 immunotherapy.
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