Tipping the immunostimulatory and inhibitory DAMP balance to harness immunogenic cell death

K. Hayashi, F. Nikolos, Y. C. Lee, A. Jain, E. Tsouko, H. Gao, A. Kasabyan, H. E. Leung, A. Osipov, S. Y. Jung, A. V. Kurtova and K. S. Chan ()
Additional contact information
K. Hayashi: Cedars-Sinai Medical Center
F. Nikolos: Cedars-Sinai Medical Center
Y. C. Lee: Taipei Medical University
A. Jain: Baylor College of Medicine
E. Tsouko: Baylor College of Medicine
H. Gao: Cedars-Sinai Medical Center
A. Kasabyan: Cedars-Sinai Medical Center
H. E. Leung: Baylor College of Medicine
A. Osipov: Cedars-Sinai Medical Center
S. Y. Jung: Baylor College of Medicine
A. V. Kurtova: Baylor College of Medicine
K. S. Chan: Cedars-Sinai Medical Center

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract Induction of tumor cell death is the therapeutic goal for most anticancer drugs. Yet, a mode of drug-induced cell death, known as immunogenic cell death (ICD), can propagate antitumoral immunity to augment therapeutic efficacy. Currently, the molecular hallmark of ICD features the release of damage-associated molecular patterns (DAMPs) by dying cancer cells. Here, we show that gemcitabine, a standard chemotherapy for various solid tumors, triggers hallmark immunostimualtory DAMP release (e.g., calreticulin, HSP70, and HMGB1); however, is unable to induce ICD. Mechanistic studies reveal gemcitabine concurrently triggers prostaglandin E2 release as an inhibitory DAMP to counterpoise the adjuvanticity of immunostimulatory DAMPs. Pharmacological blockade of prostaglandin E2 biosythesis favors CD103+ dendritic cell activation that primes a Tc1-polarized CD8+ T cell response to bolster tumor rejection. Herein, we postulate that an intricate balance between immunostimulatory and inhibitory DAMPs could determine the outcome of drug-induced ICD and pose COX-2/prostaglandin E2 blockade as a strategy to harness ICD.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (6)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-19970-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19970-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-19970-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().