Bacterial outer membrane vesicles suppress tumor by interferon-γ-mediated antitumor response.

Abstract

Gram-negative bacteria actively secrete outer membrane vesicles, spherical nano-meter-sized proteolipids enriched with outer membrane proteins, to the surroundings. Outer membrane vesicles have gained wide interests as non-living complex vaccines or delivery vehicles. However, no study has used outer membrane vesicles in treating cancer thus far. Here we investigate the potential of bacterial outer membrane vesicles as therapeutic agents to treat cancer via immunotherapy. Our results show remarkable capability of bacterial outer membrane vesicles to effectively induce long-term antitumor immune responses that can fully eradicate established tumors without notable adverse effects. Moreover, systematically administered bacterial outer membrane vesicles specifically target and accumulate in the tumor tissue, and subsequently induce the production of antitumor cytokines CXCL10 and interferon-γ. This antitumor effect is interferon-γ dependent, as interferon-γ-deficient mice could not induce such outer membrane vesicle-mediated immune response. Together, our results herein demonstrate the potential of bacterial outer membrane vesicles as effective immunotherapeutic agent that can treat various cancers without apparent adverse effects.Bacterial outer membrane vesicles (OMVs) contain immunogens but no study has yet examined their potential in treating cancer. Here, the authors demonstrate that OMVs can suppress established tumours and prevent tumour metastasis by an interferon-γ mediated antitumor response.

• Authors: Oh Youn Kim, Hyun Taek Park, Nhung Thi Hong Dinh, Seng Jin Choi, Jaewook Lee, Ji Hyun Kim, Seung-Woo Lee, Yong Song Gho
• Journal: Nature communications (Nat Commun) Vol. 8 Issue 1 Pg. 626 (09 20 2017) ISSN: 2041-1723 [Electronic] England
• PMID: 28931823 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Outer Membrane Proteins
• CXCL8 protein, human
• Chemokine CXCL10
• Cxcl10 protein, mouse
• Escherichia coli Proteins
• Interleukin-8
• Interferon-gamma
• Acyltransferases
• MsbB protein, E coli

Topics

• Acyltransferases (genetics)
• Adenocarcinoma (immunology)
• Animals
• Bacterial Outer Membrane Proteins (metabolism, pharmacology)
• Chemokine CXCL10 (drug effects, immunology)
• Colonic Neoplasms (immunology)
• Escherichia coli
• Escherichia coli Proteins (genetics)
• HEK293 Cells
• Humans
• Immunotherapy
• Interferon-gamma (drug effects, immunology)
• Interleukin-8 (drug effects, immunology)
• Mice
• Neoplasm Transplantation
• Organisms, Genetically Modified
• Transport Vesicles