The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
CD39/ENTPD1 Expression by CD4+Foxp3+ Regulatory T Cells Promotes Hepatic Metastatic Tumor Growth in Mice
Open accessAbstract
Background & Aims Adenosine mediates immune suppression and is generated by the ectonucleotidases CD39 (ENTPD1) and CD73 that are expressed on vascular endothelial cells and regulatory T cells (Treg). Although tumor-infiltrating immune cells include Foxp3+ Treg, it is not clear whether local adenosine generation by Treg promotes tumor growth in a CD39-dependent manner. In this study, we have examined the impact of CD39 expression by Treg on effector immune cell responses to hepatic metastases in vivo. Methods and Results A model of hepatic metastatic cancer was developed with portal vein infusion of luciferase-expressing melanoma B16/F10 cells and MCA38 colon cancer cells in wild type and mutant mice null for Cd39. Chimeric mice were generated by bone marrow transplantation (BMT) using Cd39 null or wild type (wt) C57BL6 donors and irradiated recipient mice. We demonstrate that hepatic growth of melanoma metastatic tumors was strongly inhibited in mice with Cd39 null vasculature or in wild type mice with circulating Cd39 null bone marrow-derived cells. We show functional CD39 expression on CD4+Foxp3+ Treg suppressed anti-tumor immunity mediated by NK cells in vitro and in vivo. Lastly, inhibition of CD39 activity by POM-1 (polyoxometalate-1), a pharmacological inhibitor of NTPDase activity, significantly inhibited tumor growth (P < .001). Conclusions CD39 expression on Treg inhibits NK activity and is permissive for metastatic growth. Pharmacological or targeted inhibition of CD39 enzymatic activity may find utility as an adjunct therapy for secondary hepatic malignancies.
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Immunogenic Cell Death in Cancer Therapy
Kroemer, G., Galluzzi, L., Kepp, O., & Zitvogel, L. (2013) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032712-100008 · Cited by 3,303
Defining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma
Sade-Feldman, M., Yizhak, K., Bjorgaard, S. L., Ray, J. P., de Boer, C. G., Jenkins, R. W., Lieb, D. J., Chen, J. H., Frederick, D. T., Barzily-Rokni, M., et al. (2018) · Cell · doi:10.1016/j.cell.2018.10.038 · Cited by 2,053
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The ectonucleotidases CD 39 and CD 73: Novel checkpoint inhibitor targets
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Metadata
- Authors
- Sun, X., Wu, Y., Gao, W., Enjyoji, K., Csizmadia, E., Müller, C. E., Murakami, T., & Robson, S. C.
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 139
- Issue
- 3
- Pages
- 1030-1040
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2029733235
- Cited by
- 279
- References
- 53
- FWCI
- 9.80
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Sun, X., Wu, Y., Gao, W., Enjyoji, K., Csizmadia, E., Müller, C. E., Murakami, T., & Robson, S. C. (2010). CD39/ENTPD1 Expression by CD4+Foxp3+ Regulatory T Cells Promotes Hepatic Metastatic Tumor Growth in Mice. Gastroenterology. https://doi.org/10.1053/j.gastro.2010.05.007
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