Frontiers in Immunology (Jun 2023)
Macrophage IL-1β contributes to tumorigenesis through paracrine AIM2 inflammasome activation in the tumor microenvironment
- Zhi Huan Chew,
- Zhi Huan Chew,
- Zhi Huan Chew,
- Zhi Huan Chew,
- Jianzhou Cui,
- Jianzhou Cui,
- Jianzhou Cui,
- Karishma Sachaphibulkij,
- Karishma Sachaphibulkij,
- Karishma Sachaphibulkij,
- Isabelle Tan,
- Isabelle Tan,
- Isabelle Tan,
- Shreya Kar,
- Shreya Kar,
- Kai Kiat Koh,
- Kai Kiat Koh,
- Kai Kiat Koh,
- Kritika Singh,
- Hong Meng Lim,
- Hong Meng Lim,
- Hong Meng Lim,
- Soo Chin Lee,
- Soo Chin Lee,
- Soo Chin Lee,
- Alan Prem Kumar,
- Alan Prem Kumar,
- Alan Prem Kumar,
- Stephan Gasser,
- Stephan Gasser,
- Stephan Gasser,
- Lina H. K. Lim,
- Lina H. K. Lim,
- Lina H. K. Lim,
- Lina H. K. Lim
Affiliations
- Zhi Huan Chew
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Zhi Huan Chew
- Immunology Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Zhi Huan Chew
- Immunology Program, Life Sciences Institute, National University of Singapore, Singapore, Singapore
- Zhi Huan Chew
- Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, Singapore
- Jianzhou Cui
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Jianzhou Cui
- Immunology Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Jianzhou Cui
- Immunology Program, Life Sciences Institute, National University of Singapore, Singapore, Singapore
- Karishma Sachaphibulkij
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Karishma Sachaphibulkij
- Immunology Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Karishma Sachaphibulkij
- Immunology Program, Life Sciences Institute, National University of Singapore, Singapore, Singapore
- Isabelle Tan
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Isabelle Tan
- Immunology Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Isabelle Tan
- Immunology Program, Life Sciences Institute, National University of Singapore, Singapore, Singapore
- Shreya Kar
- Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
- Shreya Kar
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Kai Kiat Koh
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Kai Kiat Koh
- Immunology Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Kai Kiat Koh
- Immunology Program, Life Sciences Institute, National University of Singapore, Singapore, Singapore
- Kritika Singh
- Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
- Hong Meng Lim
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Hong Meng Lim
- Immunology Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Hong Meng Lim
- Immunology Program, Life Sciences Institute, National University of Singapore, Singapore, Singapore
- Soo Chin Lee
- Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
- Soo Chin Lee
- Centre for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Soo Chin Lee
- Department of Haematology-Oncology, National University Hospital, Singapore, Singapore
- Alan Prem Kumar
- Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
- Alan Prem Kumar
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Alan Prem Kumar
- Department of Haematology-Oncology, National University Hospital, Singapore, Singapore
- Stephan Gasser
- Immunology Program, Life Sciences Institute, National University of Singapore, Singapore, Singapore
- Stephan Gasser
- Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Stephan Gasser
- 0Roche Pharma Research and Early Development, Roche Innovation Center, Roche Glycart AG, Schlieren, Switzerland
- Lina H. K. Lim
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Lina H. K. Lim
- Immunology Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Lina H. K. Lim
- Immunology Program, Life Sciences Institute, National University of Singapore, Singapore, Singapore
- Lina H. K. Lim
- Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, Singapore
- DOI
- https://doi.org/10.3389/fimmu.2023.1211730
- Journal volume & issue
-
Vol. 14
Abstract
Intracellular recognition of self and non-self -nucleic acids can result in the initiation of effective pro-inflammatory and anti-tumorigenic responses. We hypothesized that macrophages can be activated by tumor-derived nucleic acids to induce inflammasome activation in the tumor microenvironment. We show that tumor conditioned media (CM) can induce IL-1β production, indicative of inflammasome activation in primed macrophages. This could be partially dependent on caspase 1/11, AIM2 and NLRP3. IL-1β enhances tumor cell proliferation, migration and invasion while coculture of tumor cells with macrophages enhances the proliferation of tumor cells, which is AIM2 and caspase 1/11 dependent. Furthermore, we have identified that DNA-RNA hybrids could be the nucleic acid form which activates AIM2 inflammasome at a higher sensitivity as compared to dsDNA. Taken together, the tumor-secretome stimulates an innate immune pathway in macrophages which promotes paracrine cancer growth and may be a key tumorigenic pathway in cancer. Broader understanding on the mechanisms of nucleic acid recognition and interaction with innate immune signaling pathway will help us to better appreciate its potential application in diagnostic and therapeutic benefit in cancer.
Keywords
