Targeting pulmonary tumor microenvironment with CXCR4-inhibiting nanocomplex to enhance anti–PD-L1 immunotherapy

Zhaoting Li, Yixin Wang, Yuexin Shen, Chenggen Qian, David Oupicky, Minjie Sun

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish (US)
Article numbereaaz9240
JournalScience Advances
Volume6
Issue number20
DOIs
StatePublished - May 2020

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Targeting pulmonary tumor microenvironment with CXCR4-inhibiting nanocomplex to enhance anti–PD-L1 immunotherapy'. Together they form a unique fingerprint.

Cite this