Targeting Pulmonary Tumor Microenvironment with CXCR4-inhibiting Nanocomplex to Enhance Anti-PD-L1 Immunotherapy

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2020 May 23

PMID 32440550

Citations 57

Authors

Zhaoting Li

Yixin Wang

Yuexin Shen

Chenggen Qian

David Oupicky

Minjie Sun

Affiliations

Soon will be listed here.

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.

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