Anti-tumor immunity via the superoxide-eosinophil axis induced by a lipophilic component of Mycobacterium lipomannan.

Abstract

Mycobacterium bovis Bacille Calmette-Guérin (BCG) has been shown to possess potent anti-tumor activity particularly in various animal models, while the cellular and molecular mechanisms underlying its activity are not well understood. We found that lipomannan (BCG-LM), a lipophilic component of the mycobacterial cell envelope, specifically inhibits tumor growth and induces the infiltration of eosinophils at local tumor invasion sites. In contrast, neither lipoarabinomannan (BCG-LAM) nor the cell wall of Mycobacterium bovis BCG (BCG-CW) exerted anti-tumor immunity. BCG-LM enhances cytotoxic activity of eosinophils via the increased production of superoxide. Global transcriptomic analyses of BCG-LM-pulsed dendritic cells identified C-C motif ligand (CCL) 5 as a crucial chemokine for the anti-tumor immunity induced by BCG-LM, indicating that CCL5 plays an important role for the accumulation of eosinophils in the tumor microenvironment. Furthermore, BCG-LM and memory Th2 cells exerted a synergetic effect on tumor progression by cooperatively enhancing the eosinophil function. Thus, this study revealed an un-identified BCG-LM-mediated anti-tumor mechanism via superoxide produced by infiltrated eosinophils in the tumor microenvironment. Since BCG-LM activates this unique pathway, it may have potent therapeutic potential as immune cell therapy for cancer patients.

• Authors: Toshihiro Ito, Kiyoshi Hirahara, Atsushi Onodera, Ryo Koyama-Nasu, Ikuya Yano, Toshinori Nakayama
• Journal: International immunology (Int Immunol) Vol. 29 Issue 9 Pg. 411-421 (11 01 2017) ISSN: 1460-2377 [Electronic] England
• PMID: 29099969 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Japanese Society for Immunology. 2017. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Chemokine CCL5
• Lipopolysaccharides
• lipoarabinomannan
• lipomannan
• Superoxides

Topics

• Animals
• Carcinogenesis
• Cell Line, Tumor
• Cell Movement
• Cell Wall (immunology)
• Chemokine CCL5 (metabolism)
• Cytotoxicity, Immunologic
• Dendritic Cells (immunology)
• Eosinophils (immunology)
• Female
• Immunologic Memory
• Immunotherapy, Adoptive (methods)
• Lipopolysaccharides (immunology)
• Mice
• Mice, Inbred BALB C
• Mycobacterium bovis (immunology)
• Neoplasms, Experimental (immunology, therapy)
• Superoxides (metabolism)
• Th2 Cells (immunology)
• Transcriptome
• Tumor Burden
• Tumor Microenvironment