Role of neutrophil extracellular traps in radiation resistance of invasive bladder cancer

Surashri Shinde-Jadhav, Jose Joao Mansure, Roni F. Rayes, Gautier Marcq, Mina Ayoub, Rodrigo Skowronski, Ronald Kool, France Bourdeau, Fadi Brimo, Jonathan Spicer () and Wassim Kassouf ()
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Surashri Shinde-Jadhav: McGill University Health Centre
Jose Joao Mansure: McGill University Health Centre
Roni F. Rayes: McGill University Health Centre
Gautier Marcq: McGill University Health Centre
Mina Ayoub: McGill University Health Centre
Rodrigo Skowronski: McGill University Health Centre
Ronald Kool: McGill University Health Centre
France Bourdeau: McGill University Health Centre
Fadi Brimo: McGill University Health Center
Jonathan Spicer: McGill University
Wassim Kassouf: McGill University Health Centre

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Radiation therapy (RT) is used in the management of several cancers; however, tumor radioresistance remains a challenge. Polymorphonuclear neutrophils (PMNs) are recruited to the tumor immune microenvironment (TIME) post-RT and can facilitate tumor progression by forming neutrophil extracellular traps (NETs). Here, we demonstrate a role for NETs as players in tumor radioresistance. Using a syngeneic bladder cancer model, increased NET deposition is observed in the TIME of mice treated with RT and inhibition of NETs improves overall radiation response. In vitro, the protein HMGB1 promotes NET formation through a TLR4-dependent manner and in vivo, inhibition of both HMGB1 and NETs significantly delays tumor growth. Finally, NETs are observed in bladder tumors of patients who did not respond to RT and had persistent disease post-RT, wherein a high tumoral PMN-to-CD8 ratio is associated with worse overall survival. Together, these findings identify NETs as a potential therapeutic target to increase radiation efficacy.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23086-z

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DOI: 10.1038/s41467-021-23086-z

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