The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index.
IL-2 and IL-21 confer opposing differentiation programs to CD8+ T cells for adoptive immunotherapy
Open accessAbstract
IL-2 and IL-21 are closely related cytokines that might have arisen by gene duplication. Both cytokines promote the function of effector CD8+ T cells, but their distinct effects on antigen-driven differentiation of naive CD8+ T cells into effector CD8+ T cells are not clearly understood. We found that antigen-induced expression of Eomesodermin (Eomes) and maturation of naive CD8+ T cells into granzyme B- and CD44-expressing effector CD8+ T cells was enhanced by IL-2, but, unexpectedly, suppressed by IL-21. Furthermore, IL-21 repressed expression of IL-2Ra and inhibited IL-2–mediated acquisition of a cytolytic CD8+ T-cell phenotype. Despite its inhibitory effects, IL-21 did not induce anergy, but instead potently enhanced the capacity of cells to mediate tumor regression upon adoptive transfer. In contrast, IL-2 impaired the subsequent antitumor function of transferred cells. Gene expression studies revealed a distinct IL-21 program that was characterized phenotypically by increased expression of L-selectin and functionally by enhanced antitumor immunity that was not reversed by secondary in vitro stimulation with antigen and IL-2. Thus, the efficacy of CD8+ T cells for adoptive immunotherapy can be influenced by opposing differentiation programs conferred by IL-2 and IL-21, a finding with important implications for the development of cellular cancer therapies.
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Cites
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Self-citationCancer regression in patients after transfer of genetically engineered lymphocytes
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Self-citationEffector and memory CD8+ T cell fate coupled by T-bet and eomesodermin
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Cited by
Adoptive immunotherapy for cancer: harnessing the T cell response
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Self-citationLong-term outcomes following CAR T cell therapy: what we know so far
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Wnt signaling arrests effector T cell differentiation and generates CD8+ memory stem cells
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“Additional improvements in the cell manufacturing process might be achieved using cytokines, such as IL-7, IL-21, and/or IL-15, that have been reported to improve the growth of human T cells in vitro and enhance the therapeutic efficacy of adoptively transferred murine T cells in preclinical models (15, 19, 20).”
BackgroundMetabolic Regulation of T Cell Longevity and Function in Tumor Immunotherapy
Kishton, R. J., Sukumar, M., & Restifo, N. P. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.06.016 · Cited by 548
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Metadata
- Authors
- Hinrichs, C. S., Spolski, R., Paulos, C. M., Gattinoni, L., Kerstann, K. W., Palmer, D. C., Klebanoff, C. A., Rosenberg, S. A., Leonard, W. J., & Restifo, N. P.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2008-06-01
- Volume
- 111
- Issue
- 11
- Pages
- 5326-5333
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2050297562
- Cited by
- 462
- References
- 65
- FWCI
- 11.99
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Hinrichs, C. S., Spolski, R., Paulos, C. M., Gattinoni, L., Kerstann, K. W., Palmer, D. C., Klebanoff, C. A., Rosenberg, S. A., Leonard, W. J., & Restifo, N. P. (2008). IL-2 and IL-21 confer opposing differentiation programs to CD8+ T cells for adoptive immunotherapy. Blood. https://doi.org/10.1182/blood-2007-09-113050
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