Abstract:
: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.
journal_name
Sci Advjournal_title
Science advancesauthors
Li Z,Wang Y,Shen Y,Qian C,Oupicky D,Sun Mdoi
10.1126/sciadv.aaz9240subject
Has Abstractpub_date
2020-05-15 00:00:00pages
eaaz9240issue
20issn
2375-2548pii
aaz9240journal_volume
6pub_type
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