The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
CD39 Expression Defines Cell Exhaustion in Tumor-Infiltrating CD8+ T Cells
Open accessAbstract
The ability of CD8+ T lymphocytes to eliminate tumors is limited by their ability to engender an immunosuppressive microenvironment. Here we describe a subset of tumor-infiltrating CD8+ T cells marked by high expression of the immunosuppressive ATP ecto-nucleotidase CD39. The frequency of CD39highCD8+ T cells increased with tumor growth but was absent in lymphoid organs. Tumor-infiltrating CD8+ T cells with high CD39 expression exhibited features of exhaustion, such as reduced production of TNF and IL2 and expression of coinhibitory receptors. Exhausted CD39+CD8+ T cells from mice hydrolyzed extracellular ATP, confirming that CD39 is enzymatically active. Furthermore, exhausted CD39+CD8+ T cells inhibited IFNγ production by responder CD8+ T cells. In specimens from breast cancer and melanoma patients, CD39+CD8+ T cells were present within tumors and invaded or metastatic lymph nodes, but were barely detectable within noninvaded lymph nodes and absent in peripheral blood. These cells exhibited an exhausted phenotype with impaired production of IFNγ, TNF, IL2, and high expression of coinhibitory receptors. Although T-cell receptor engagement was sufficient to induce CD39 on human CD8+ T cells, exposure to IL6 and IL27 promoted CD39 expression on stimulated CD8+ T cells from human or murine sources. Our findings show how the tumor microenvironment drives the acquisition of CD39 as an immune regulatory molecule on CD8+ T cells, with implications for defining a biomarker of T-cell dysfunction and a target for immunotherapeutic intervention. Significance: The tumor microenvironment elicits a subset of functionally exhausted CD8+ T cells by creating conditions that induce cell surface expression of CD39, an immunosuppressive molecule that can be therapeutically targeted to restore effector T-cell function. Cancer Res; 78(1); 115–28. ©2017 AACR.
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Cites
Cancer Immunoediting: Integrating Immunity’s Roles in Cancer Suppression and Promotion
Schreiber, R. D., Old, L. J., & Smyth, M. J. (2011) · Science · doi:10.1126/science.1203486 · Cited by 6,474
The immune contexture in human tumours: impact on clinical outcome
Fridman, W. H., Pagès, F., Sautès-Fridman, C., & Galon, J. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3245 · Cited by 4,981
Immune Checkpoint Blockade: A Common Denominator Approach to Cancer Therapy
Topalian, S. L., Drake, C. G., & Pardoll, D. M. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.03.001 · Cited by 4,229
Wherry, E. J. (2011) · Nature Immunology · doi:10.1038/ni.2035 · Cited by 4,062 · cited 6×
“Two cardinal features of exhausted CD8 T cells are the gradual loss of effector cytokine production and sustained expression of multiple inhibitory receptors (iRs) such as PD-1, LAG-3 and Tim-3 (10).”
BackgroundInfluentialMetabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression
Chang, C.-H., Qiu, J., O’Sullivan, D., Buck, M. D., Noguchi, T., Curtis, J. D., Chen, Q., Gindin, M., Gubin, M. M., van der Windt, G. J. W., et al. (2015) · Cell · doi:10.1016/j.cell.2015.08.016 · Cited by 3,331
Deaglio, S., Dwyer, K. M., Gao, W., Friedman, D., Usheva, A., Erat, A., Chen, J.-F., Enjyoji, K., Linden, J., Oukka, M., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20062512 · Cited by 2,470
Natural Innate and Adaptive Immunity to Cancer
Vesely, M. D., Kershaw, M. H., Schreiber, R. D., & Smyth, M. J. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101324 · Cited by 2,101
Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity
Sakuishi, K., Apetoh, L., Sullivan, J. M., Blazar, B. R., Kuchroo, V. K., & Anderson, A. C. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20100643 · Cited by 2,072
Blackburn, S. D., Shin, H., Haining, W. N., Zou, T., Workman, C. J., Polley, A., Betts, M. R., Freeman, G. J., Vignali, D. A. A., & Wherry, E. J. (2009) · Nature Immunology · doi:10.1038/ni.1679 · Cited by 2,062
Spranger, S., Spaapen, R. M., Zha, Y., Williams, J., Meng, Y., Ha, T. T., & Gajewski, T. F. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3006504 · Cited by 1,677
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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
Bystander CD8+ T cells are abundant and phenotypically distinct in human tumour infiltrates
Simoni, Y., Becht, E., Fehlings, M., Loh, C. Y., Koo, S.-L., Teng, K. W. W., Yeong, J. P. S., Nahar, R., Zhang, T., Kared, H., et al. (2018) · Nature · doi:10.1038/s41586-018-0130-2 · Cited by 1,370
Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors
Duhen, T., Duhen, R., Montler, R., Moses, J., Moudgil, T., de Miranda, N. F., Goodall, C. P., Blair, T. C., Fox, B. A., McDermott, J. E., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05072-0 · Cited by 938
Targeting adenosine for cancer immunotherapy
Leone, R. D., & Emens, L. A. (2018) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-018-0360-8 · Cited by 543
Association of COVID-19 inflammation with activation of the C5a–C5aR1 axis
Carvelli, J., Demaria, O., Vély, F., Batista, L., Chouaki Benmansour, N., Fares, J., Carpentier, S., Thibult, M.-L., Morel, A., Remark, R., et al. (2020) · Nature · doi:10.1038/s41586-020-2600-6 · Cited by 526
Metadata
- Authors
- Canale, F. P., Ramello, M. C., Núñez, N., Furlan, C. L. A., Bossio, S. N., Serrán, M. G., Boari, J. T., del Castillo, A., Ledesma, M., Sedlik, C., Piaggio, E., Gruppi, A., Rodríguez, E. V. A., & Montes, C. L.
- Venue
- Cancer Research
- Published
- 2018-01-01
- Volume
- 78
- Issue
- 1
- Pages
- 115-128
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2766745368
- Cited by
- 408
- References
- 43
- FWCI
- 16.03
- Type
- journal article
- Language
- en
- Open access
- green
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- Canale, F. P., Ramello, M. C., Núñez, N., Furlan, C. L. A., Bossio, S. N., Serrán, M. G., Boari, J. T., del Castillo, A., Ledesma, M., Sedlik, C., Piaggio, E., Gruppi, A., Rodríguez, E. V. A., & Montes, C. L. (2018). CD39 Expression Defines Cell Exhaustion in Tumor-Infiltrating CD8+ T Cells. Cancer Research. https://doi.org/10.1158/0008-5472.can-16-2684
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