Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-23086-z
Keywords
-
Categories
Ask authors/readers for more resources
Radioresistance in bladder cancer treatment is linked to the recruitment of neutrophil extracellular traps (NETs) to the tumor immune microenvironment post-radiation therapy, as demonstrated in a mouse model. Inhibition of NETs can improve radiation response, suggesting NETs as a potential therapeutic target to enhance radiation efficacy.
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. Radioresistance remains a challenge in the treatment of bladder cancer. In this study, the authors show in mice that radiation increases deposits of neutrophil extracellular traps (NETs) via a TLR4-dependent mechanism and that NETs-targeting strategies can improve the response to radiotherapy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available