Expression of arginase I in myeloid cells limits control of residual disease after radiation therapy of tumors in mice
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 h...
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| Format: | Article |
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Radiation Research Society
2014
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| Online Access: | https://eprints.nottingham.ac.uk/33654/ |
| _version_ | 1848794674844663808 |
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| author | Crittenden, Marka R. Savage, Talicia Cottam, Benjamin Baird, Jason Rodriguez, Paulo C. Newell, Pippa Young, Kristina Jackson, Andrew M. Gough, Michael J. |
| author_facet | Crittenden, Marka R. Savage, Talicia Cottam, Benjamin Baird, Jason Rodriguez, Paulo C. Newell, Pippa Young, Kristina Jackson, Andrew M. Gough, Michael J. |
| author_sort | Crittenden, Marka R. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:19:57Z |
| format | Article |
| id | nottingham-33654 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:19:57Z |
| publishDate | 2014 |
| publisher | Radiation Research Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-336542020-05-04T16:49:59Z https://eprints.nottingham.ac.uk/33654/ 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. 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. Radiation Research Society 2014-08-01 Article PeerReviewed Crittenden, Marka R., Savage, Talicia, Cottam, Benjamin, Baird, Jason, Rodriguez, Paulo C., Newell, Pippa, Young, Kristina, Jackson, Andrew M. and Gough, Michael 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). pp. 182-90. ISSN 1938-5404 http://www.bioone.org/doi/10.1667/RR13493.1 doi:10.1667/RR13493.1 doi:10.1667/RR13493.1 |
| spellingShingle | Crittenden, Marka R. Savage, Talicia Cottam, Benjamin Baird, Jason Rodriguez, Paulo C. Newell, Pippa Young, Kristina Jackson, Andrew M. Gough, Michael J. Expression of arginase I in myeloid cells limits control of residual disease after radiation therapy of tumors in mice |
| title | Expression of arginase I in myeloid cells limits control of residual disease after radiation therapy of tumors in mice |
| title_full | Expression of arginase I in myeloid cells limits control of residual disease after radiation therapy of tumors in mice |
| title_fullStr | Expression of arginase I in myeloid cells limits control of residual disease after radiation therapy of tumors in mice |
| title_full_unstemmed | Expression of arginase I in myeloid cells limits control of residual disease after radiation therapy of tumors in mice |
| title_short | Expression of arginase I in myeloid cells limits control of residual disease after radiation therapy of tumors in mice |
| title_sort | expression of arginase i in myeloid cells limits control of residual disease after radiation therapy of tumors in mice |
| url | https://eprints.nottingham.ac.uk/33654/ https://eprints.nottingham.ac.uk/33654/ https://eprints.nottingham.ac.uk/33654/ |