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.

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.

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

• Journal Article Type: Article
• Acceptance Date: Dec 1, 2013
• Online Publication Date: Jul 3, 2014
• Publication Date: 2014-08
• Deposit Date: May 31, 2016
• 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
• DOI: https://doi.org/10.1667/rr13493.1
• Public URL: https://nottingham-repository.worktribe.com/output/731297
• Publisher URL: http://www.bioone.org/doi/10.1667/RR13493.1