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Neutrophils promote tumor resistance to radiation therapy.

Publication ,  Journal Article
Wisdom, AJ; Hong, CS; Lin, AJ; Xiang, Y; Cooper, DE; Zhang, J; Xu, ES; Kuo, H-C; Mowery, YM; Carpenter, DJ; Kadakia, KT; Himes, JE; Luo, L ...
Published in: Proc Natl Acad Sci U S A
September 10, 2019

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.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

September 10, 2019

Volume

116

Issue

37

Start / End Page

18584 / 18589

Location

United States

Related Subject Headings

  • Young Adult
  • Whole-Body Irradiation
  • Uterine Cervical Neoplasms
  • Sarcoma
  • Retrospective Studies
  • Radiation Tolerance
  • Neutrophils
  • Middle Aged
  • Mice, Transgenic
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
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Wisdom, A. J., Hong, C. S., Lin, A. J., Xiang, Y., Cooper, D. E., Zhang, J., … Kirsch, D. G. (2019). Neutrophils promote tumor resistance to radiation therapy. Proc Natl Acad Sci U S A, 116(37), 18584–18589. https://doi.org/10.1073/pnas.1901562116
Wisdom, Amy J., Cierra S. Hong, Alexander J. Lin, Yu Xiang, Daniel E. Cooper, Jin Zhang, Eric S. Xu, et al. “Neutrophils promote tumor resistance to radiation therapy.Proc Natl Acad Sci U S A 116, no. 37 (September 10, 2019): 18584–89. https://doi.org/10.1073/pnas.1901562116.
Wisdom AJ, Hong CS, Lin AJ, Xiang Y, Cooper DE, Zhang J, et al. Neutrophils promote tumor resistance to radiation therapy. Proc Natl Acad Sci U S A. 2019 Sep 10;116(37):18584–9.
Wisdom, Amy J., et al. “Neutrophils promote tumor resistance to radiation therapy.Proc Natl Acad Sci U S A, vol. 116, no. 37, Sept. 2019, pp. 18584–89. Pubmed, doi:10.1073/pnas.1901562116.
Wisdom AJ, Hong CS, Lin AJ, Xiang Y, Cooper DE, Zhang J, Xu ES, Kuo H-C, Mowery YM, Carpenter DJ, Kadakia KT, Himes JE, Luo L, Ma Y, Williams N, Cardona DM, Haldar M, Diao Y, Markovina S, Schwarz JK, Kirsch DG. Neutrophils promote tumor resistance to radiation therapy. Proc Natl Acad Sci U S A. 2019 Sep 10;116(37):18584–18589.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

September 10, 2019

Volume

116

Issue

37

Start / End Page

18584 / 18589

Location

United States

Related Subject Headings

  • Young Adult
  • Whole-Body Irradiation
  • Uterine Cervical Neoplasms
  • Sarcoma
  • Retrospective Studies
  • Radiation Tolerance
  • Neutrophils
  • Middle Aged
  • Mice, Transgenic
  • Mice