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Expression of Arginase I in Myeloid Cells Limits Control of Residual Disease after Radiation Therapy of Tumors in Mice

Crittenden, Marka R.; Savage, Talicia; Cottam, Benjamin; Baird, Jason; Rodriguez, Paulo C.; Newell, Pippa; Young, Kristina; Jackson, Andrew M.; Gough, Michael J.

Authors

Marka R. Crittenden

Talicia Savage

Benjamin Cottam

Jason Baird

Paulo C. Rodriguez

Pippa Newell

Kristina Young

Michael J. Gough



Abstract

An accumulating body of evidence demonstrates that radiation therapy can generate adaptive immune responses that contribute to tumor control. However, in the absence of additional immune therapy, the adaptive immune response is insufficient to prevent tumor recurrence or affect distant disease. It has been shown in multiple models that tumor-infiltrating myeloid cells exhibit alternative activation phenotypes and are able to suppress adaptive immune responses, and recent data suggests that the myeloid response in tumors treated with cytotoxic therapy limits tumor control. We hypothesized that tumor myeloid cells inhibit the adaptive immune response after radiation therapy through expression of the enzyme arginase I. Using a myeloid cell-specific deletion of arginase I in mice, we demonstrate an improved tumor control after radiation therapy. However, tumors still recurred despite the conditional knockdown of arginase I. Since multiple alternative factors may combine to inhibit adaptive immunity, we propose that targeting macrophage differentiation may be a more effective strategy than targeting individual suppressive pathways.

Journal Article Type Article
Publication Date 2014-08
Journal Radiation Research
Print ISSN 0033-7587
Electronic ISSN 1938-5404
Publisher Radiation Research Society
Peer Reviewed Peer Reviewed
Volume 182
Issue 2
Pages 182-190
APA6 Citation Crittenden, M. R., Savage, T., Cottam, B., Baird, J., Rodriguez, P. C., Newell, P., …Gough, M. J. (2014). Expression of Arginase I in Myeloid Cells Limits Control of Residual Disease after Radiation Therapy of Tumors in Mice. Radiation Research, 182(2), 182-190. https://doi.org/10.1667/rr13493.1
DOI https://doi.org/10.1667/rr13493.1
Publisher URL http://www.bioone.org/doi/10.1667/RR13493.1
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf
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