Back to Search Start Over

Neutrophils promote tumor resistance to radiation therapy

Authors :
Jonathon E. Himes
Jin Zhang
Yvonne M. Mowery
Yan Ma
Amy J. Wisdom
Hsuan-Cheng Kuo
Yu Xiang
Lixia Luo
David G. Kirsch
Julie K. Schwarz
David Carpenter
Alexander J. Lin
Yarui Diao
Cierra S. Hong
Eric S. Xu
Diana M. Cardona
Daniel E. Cooper
Malay Haldar
Stephanie Markovina
Nerissa Williams
Kushal T. Kadakia
Source :
Proceedings of the National Academy of Sciences. 116:18584-18589
Publication Year :
2019
Publisher :
Proceedings of the National Academy of Sciences, 2019.

Abstract

Nearly two-thirds of cancer patients are treated with radiation therapy (RT), often with the intent to achieve complete and permanent tumor regression (local control). RT is the primary treatment modality used to achieve local control for many malignancies, including locally advanced cervical cancer, head and neck cancer, and lung cancer. The addition of concurrent platinum-based radiosensitizing chemotherapy improves local control and patient survival. Enhanced outcomes with concurrent chemoradiotherapy may result from increased direct killing of tumor cells and effects on nontumor cell populations. Many patients treated with concurrent chemoradiotherapy exhibit a decline in neutrophil count, but the effects of neutrophils on radiation therapy are controversial. To investigate the clinical significance of neutrophils in the response to RT, we examined patient outcomes and circulating neutrophil counts in cervical cancer patients treated with definitive chemoradiation. Although pretreatment neutrophil count did not correlate with outcome, lower absolute neutrophil count after starting concurrent chemoradiotherapy was associated with higher rates of local control, metastasis-free survival, and overall survival. To define the role of neutrophils in tumor response to RT, we used genetic and pharmacological approaches to deplete neutrophils in an autochthonous mouse model of soft tissue sarcoma. Neutrophil depletion prior to image-guided focal irradiation improved tumor response to RT. Our results indicate that neutrophils promote resistance to radiation therapy. The efficacy of chemoradiotherapy may depend on the impact of treatment on peripheral neutrophil count, which has the potential to serve as an inexpensive and widely available biomarker.

Details

ISSN :
10916490 and 00278424
Volume :
116
Database :
OpenAIRE
Journal :
Proceedings of the National Academy of Sciences
Accession number :
edsair.doi.dedup.....1cd578a5a4abbd86fd4f7f6178a3d254
Full Text :
https://doi.org/10.1073/pnas.1901562116