Work published in Nature Communications demonstrates a critical role for neutrophil extracellular traps (NETs) in radioresistance
SOURCE: RI-MUHC. Published in Nature Communications, a new study by researchers from the Research Institute of the McGill University Health Centre (RI-MUHC) may lead to changes in radiation therapy for treatment of bladder cancer. Led by Wassim Kassouf, MD, a surgeon at the MUHC and senior scientist at the RI-MUHC and in collaboration with Jonathan Spicer, MD, PhD, this study has shown that extracellular complexes of DNA known as neutrophil extracellular traps (NETs) may be a target to reduce tumour radioresistance.
Bladder cancer is the tenth most common cause of cancer-related deaths worldwide. Radiation therapy is commonly used in the management of bladder cancers, particularly in cases where surgery is not possible. However, the resistance of some tumours to this radiation remains a challenge. Researchers in this area study a cell type known as polymorphonuclear neutrophils (PMNs), which concentrate in an irradiated tissue and are linked to poor prognosis after radiation. PMNs facilitate tumour progression by forming neutrophil extracellular traps (NETs) after radiation therapy.
“We observed that by inhibiting the formation of NETs, we were able to improve the overall response to radiation in model organisms,” says Dr. Kassouf, who is a member of the Cancer Research Program and conducts research at the Centre for Translational Biology at the RI‑MUHC. “Additionally, we saw significant delays in tumour growth when we inhibited NET formation.”
“This is important because NETs are observed in bladder tumours of patients who do not respond to radiation therapy,” adds Jose Mansure, PhD, a research associate working with Dr. Kassouf.
Surashri Shinde, first author of the study, conducts doctoral work in Dr. Kassouf’s laboratory, co-supervised by Dr. Spicer. “Our findings identify NETs as a potential therapeutic target to increase radiation efficacy and ultimately, improve overall survival for patients with bladder cancer and other solid tumours,” she says.
About the study:
Read the publication, selected as one of the Editor’s Highlights in Cancer in Nature Communications.
The authors gratefully acknowledge funding from the Canadian Institutes of Health Research.
The authors thank the Histopathology and Molecular Imaging technology platforms of the RI‑MUHC for services in multiplex-IHC staining and microscopy.
June 2, 2021