The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
PD-L1 blockade synergizes with IL-2 therapy in reinvigorating exhausted T cells
Open accessAbstract
The inhibitory receptor programmed cell death 1 (PD-1) plays a major role in functional exhaustion of T cells during chronic infections and cancer, and recent clinical data suggest that blockade of the PD-1 pathway is an effective immunotherapy in treating certain cancers. Thus, it is important to define combinatorial approaches that increase the efficacy of PD-1 blockade. To address this issue, we examined the effect of IL-2 and PD-1 ligand 1 (PD-L1) blockade in the mouse model of chronic lymphocytic choriomeningitis virus (LCMV) infection. We found that low-dose IL-2 administration alone enhanced CD8+ T cell responses in chronically infected mice. IL-2 treatment also decreased inhibitory receptor levels on virus-specific CD8+ T cells and increased expression of CD127 and CD44, resulting in a phenotype resembling that of memory T cells. Surprisingly, IL-2 therapy had only a minimal effect on reducing viral load. However, combining IL-2 treatment with blockade of the PD-1 inhibitory pathway had striking synergistic effects in enhancing virus-specific CD8+ T cell responses and decreasing viral load. Interestingly, this reduction in viral load occurred despite increased numbers of Tregs. These results suggest that combined IL-2 therapy and PD-L1 blockade merits consideration as a regimen for treating human chronic infections and cancer.
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Citations
Cites
Safety, activity, and immune correlates of anti–PD-1 antibody in cancer
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PD-1 and Its Ligands in Tolerance and Immunity
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Self-citationTumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion
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Wherry, E. J. (2011) · Nature Immunology · doi:10.1038/ni.2035 · Cited by 4,062 · cited 3×
“cells are molecularly distinct from naive, effector, or memory CD8 T cells (2, 42).”
InfluentialPD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression
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Self-citationMolecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
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Self-citationPreferential Localization of Effector Memory Cells in Nonlymphoid Tissue
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“press CD127 are preferentially destined to become memory CD8 T cells (50).”
Self-citationUpregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction
Trautmann, L., Janbazian, L., Chomont, N., Said, E. A., Gimmig, S., Bessette, B., Boulassel, M.-R., Delwart, E., Sepulveda, H., Balderas, R. S., et al. (2006) · Nature Medicine · doi:10.1038/nm1482 · Cited by 1,565
Cited by
Oncology meets immunology: the cancer-immunity cycle.
Chen, D. S., & Mellman, I. (2013) · Immunity · doi:10.1016/j.immuni.2013.07.012 · Cited by 6,929
Molecular and cellular insights into T cell exhaustion
Wherry, E. J., & Kurachi, M. (2015) · Nature Reviews Immunology · doi:10.1038/nri3862 · Cited by 4,652
Metabolic 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
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Hotchkiss, R. S., Moldawer, L. L., Opal, S. M., Reinhart, K., Turnbull, I. R., & Vincent, J.-L. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.45 · Cited by 1,620
Metadata
- Authors
- West, E. E., Jin, H.-T., Rasheed, A.-U., Penaloza-MacMaster, P., Ha, S.-J., Tan, W. G., Youngblood, B., Freeman, G. J., Smith, K. A., & Ahmed, R.
- Venue
- Journal of Clinical Investigation
- Published
- 2013-05-15
- Volume
- 123
- Issue
- 6
- Pages
- 2604-2615
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2043579427
- Cited by
- 298
- References
- 11
- FWCI
- 12.02
- Type
- journal article
- Language
- en
- Open access
- bronze
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- West, E. E., Jin, H.-T., Rasheed, A.-U., Penaloza-MacMaster, P., Ha, S.-J., Tan, W. G., Youngblood, B., Freeman, G. J., Smith, K. A., & Ahmed, R. (2013). PD-L1 blockade synergizes with IL-2 therapy in reinvigorating exhausted T cells. Journal of Clinical Investigation. https://doi.org/10.1172/jci67008
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
