Premium
Trapping of Lipopolysaccharide to Promote Immunotherapy against Colorectal Cancer and Attenuate Liver Metastasis
Author(s) -
Song Wantong,
Tiruthani Karthik,
Wang Ying,
Shen Limei,
Hu Mengying,
Dorosheva Oleksandra,
Qiu Kunyu,
Kinghorn Karina A.,
Liu Rihe,
Huang Leaf
Publication year - 2018
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.201805007
Subject(s) - cancer research , lipopolysaccharide , immunotherapy , colorectal cancer , metastasis , tumor microenvironment , microbiome , cancer immunotherapy , immune system , medicine , immunology , cancer , biology , bioinformatics
The development and progression of colorectal cancer (CRC) is closely related to gut microbiome. Here, the impact of lipopolysaccharide (LPS), one of the most prevalent products in the gut microbiome, on CRC immunotherapy is investigated. It is found that LPS is abundant in orthotopic CRC tissue and is associated with low responses to anti‐PD‐L1 mAb therapy, and clearance of Gram‐negative bacteria from the gut using polymyxin B (PmB) or blockade of Toll‐like receptor 4 using TAK‐242 will both relieve the immunosuppressive microenvironment and boost T‐cell infiltration into the CRC tumor. Further, an engineered LPS‐targeting fusion protein is designed and its coding sequence is loaded into a lipid–protamine–DNA (LPD) nanoparticle system for selective expression of LPS trap protein and blocking LPS inside the tumor, and this nanotrapping system significantly relieves the immunosuppressive microenvironment and boosts anti‐PD‐L1 mAb therapy against CRC tumors. This LPS trap system even attenuates CRC liver metastasis when applied, suggesting the importance of blocking LPS in the gut–liver axis. The strategy applied here may provide a useful new way for treating CRC as well as other epithelial cancers that interact with mucosa microbiome.