Neutrophils are Mediators of Metastatic Prostate Cancer Progression in Bone

Authors

Diane L. Costanzo-Garvey, University of Nebraska Medical CenterFollow
Tyler Keeley, University of Nebraska Medical Center
Adam J. Case, University of Nebraska Medical CenterFollow
Gabrielle F. Watson, University of Nebraska Medical CenterFollow
Massar Alsamraae, University of Nebraska Medical CenterFollow
Yangsheng Yu, University of Nebraska Medical CenterFollow
Kaihong Su, University of Nebraska Medical CenterFollow
Cortney E. Heim, University of Nebraska Medical CenterFollow
Tammy Kielian, University of Nebraska Medical CenterFollow
Colm Morrissey, University of Washington
Jeremy S Frieling, H. Lee Moffitt Cancer Center and Research Institute
Leah M. Cook, University of Nebraska Medical CenterFollow

Document Type

Article

Journal Title

Cancer Immunology, Immunotherapy

Publication Date

2020

Volume

69

Abstract

Bone metastatic prostate cancer (BM-PCa) significantly reduces overall patient survival and is currently incurable. Current standard immunotherapy showed promising results for PCa patients with metastatic, but less advanced, disease (i.e., fewer than 20 bone lesions) suggesting that PCa growth in bone contributes to response to immunotherapy. We found that: (1) PCa stimulates recruitment of neutrophils, the most abundant immune cell in bone, and (2) that neutrophils heavily infiltrate regions of prostate tumor in bone of BM-PCa patients. Based on these findings, we examined the impact of direct neutrophil-prostate cancer interactions on prostate cancer growth. Bone marrow neutrophils directly induced apoptosis of PCa in vitro and in vivo, such that neutrophil depletion in bone metastasis models enhanced BM-PCa growth. Neutrophil-mediated PCa killing was found to be mediated by suppression of STAT5, a transcription factor shown to promote PCa progression. However, as the tumor progressed in bone over time, neutrophils from late-stage bone tumors failed to elicit cytotoxic effector responses to PCa. These findings are the first to demonstrate that bone-resident neutrophils inhibit PCa and that BM-PCa are able to progress via evasion of neutrophil-mediated killing. Enhancing neutrophil cytotoxicity in bone may present a novel therapeutic option for bone metastatic prostate cancer.

DOI Link

10.1007/s00262-020-02527-6

ISSN

1432-0851

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Costanzo-Garvey, Diane L.; Keeley, Tyler; Case, Adam J.; Watson, Gabrielle F.; Alsamraae, Massar; Yu, Yangsheng; Su, Kaihong; Heim, Cortney E.; Kielian, Tammy; Morrissey, Colm; Frieling, Jeremy S; and Cook, Leah M., "Neutrophils are Mediators of Metastatic Prostate Cancer Progression in Bone" (2020). Journal Articles: Pathology and Microbiology. 73.
https://digitalcommons.unmc.edu/com_pathmicro_articles/73