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Neutrophils promote tumor resistance to radiation therapy
- 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.
- Subjects :
- Adult
Oncology
medicine.medical_specialty
Adolescent
Neutrophils
medicine.medical_treatment
Uterine Cervical Neoplasms
Mice, Transgenic
Kaplan-Meier Estimate
Radiation Tolerance
Disease-Free Survival
Leukocyte Count
Mice
Young Adult
Internal medicine
medicine
Animals
Humans
Lung cancer
Aged
Retrospective Studies
Aged, 80 and over
Cervical cancer
Chemotherapy
Multidisciplinary
business.industry
Head and neck cancer
Cancer
Sarcoma
Chemoradiotherapy
Biological Sciences
Middle Aged
medicine.disease
Radiation therapy
Disease Models, Animal
Absolute neutrophil count
Female
business
Whole-Body Irradiation
Subjects
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