The DOI matches its Crossref record; 77 of the 77 references it cites were found in a registry or an index.
Dual Blockade of PD-1 and CTLA-4 Combined with Tumor Vaccine Effectively Restores T-Cell Rejection Function in Tumors
Open accessAbstract
Tumor progression is facilitated by regulatory T cells (Treg) and restricted by effector T cells. In this study, we document parallel regulation of CD8+ T cells and Foxp3+ Tregs by programmed death-1 (PD-1, PDCD1). In addition, we identify an additional role of CTL antigen-4 (CTLA-4) inhibitory receptor in further promoting dysfunction of CD8+ T effector cells in tumor models (CT26 colon carcinoma and ID8-VEGF ovarian carcinoma). Two thirds of CD8+ tumor-infiltrating lymphocytes (TIL) expressed PD-1, whereas one third to half of CD8+ TIL coexpressed PD-1 and CTLA-4. Double-positive (PD-1+CTLA-4+) CD8+ TIL had characteristics of more severe dysfunction than single-positive (PD-1+ or CTLA-4+) TIL, including an inability to proliferate and secrete effector cytokines. Blockade of both PD-1 and CTLA-4 resulted in reversal of CD8+ TIL dysfunction and led to tumor rejection in two thirds of mice. Double blockade was associated with increased proliferation of antigen-specific effector CD8+ and CD4+ T cells, antigen-specific cytokine release, inhibition of suppressive functions of Tregs, and upregulation of key signaling molecules critical for T-cell function. When used in combination with GVAX vaccination (consisting of granulocyte macrophage colony-stimulating factor–expressing irradiated tumor cells), inhibitory pathway blockade induced rejection of CT26 tumors in 100% of mice and ID8-VEGF tumors in 75% of mice. Our study indicates that PD-1 signaling in tumors is required for both suppressing effector T cells and maintaining tumor Tregs, and that PD-1/PD-L1 pathway (CD274) blockade augments tumor inhibition by increasing effector T-cell activity, thereby attenuating Treg suppression. Cancer Res; 73(12); 3591–603. ©2013 AACR.
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Cites
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J. C., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1003466 · Cited by 15,155
Safety, activity, and immune correlates of anti–PD-1 antibody in cancer
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Safety and activity of anti-PD-L1 antibody in patients with advanced cancer
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PD-1 and Its Ligands in Tolerance and Immunity
Keir, M. E., Butte, M. J., Freeman, G. J., & Sharpe, A. H. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090331 · Cited by 5,378
Self-citationTumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion
Dong, H., Strome, S. E., Salomao, D. R., Tamura, H., Hirano, F., Flies, D. B., Roche, P. C., Lu, J., Zhu, G., Tamada, K., et al. (2002) · Nature Medicine · doi:10.1038/nm730 · Cited by 5,025
Restoring function in exhausted CD8 T cells during chronic viral infection
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Self-citationSakaguchi, S. (2004) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.141122 · Cited by 3,306
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CTLA-4 Control over Foxp3 + Regulatory T Cell Function
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CD4+CD25+ suppressor T cells: more questions than answers
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Gubin, M. M., Zhang, X., Schuster, H., Caron, E., Ward, J. P., Noguchi, T., Ivanova, Y., Hundal, J., Arthur, C. D., Krebber, W.-J., et al. (2014) · Nature · doi:10.1038/nature13988 · Cited by 1,974
“…and renders the host more susceptible to autoimmunity 13,22,23 ; α PD-1 promotes T cell activation acting as a rheostat of immune effector function 9,22,24,25 ; and (c) dual blockade of CTLA-4 and PD-1 is particularly effective in promoting enhanced anti-tumour effector functions 10,22,26 .”
Self-citationThommen, D. S., & Schumacher, T. N. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.012 · Cited by 1,299
In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target
Manguso, R. T., Pope, H. W., Zimmer, M. D., Brown, F. D., Yates, K. B., Miller, B. C., Collins, N. B., Bi, K., LaFleur, M. W., Juneja, V. R., et al. (2017) · Nature · doi:10.1038/nature23270 · Cited by 1,147
Metadata
- Authors
- Duraiswamy, J., Kaluza, K. M., Freeman, G. J., & Coukos, G.
- Venue
- Cancer Research
- Published
- 2013-06-13
- Volume
- 73
- Issue
- 12
- Pages
- 3591-3603
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2150640296
- Cited by
- 745
- References
- 77
- FWCI
- 36.99
- Type
- journal article
- Language
- en
- Open access
- green
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- Duraiswamy, J., Kaluza, K. M., Freeman, G. J., & Coukos, G. (2013). Dual Blockade of PD-1 and CTLA-4 Combined with Tumor Vaccine Effectively Restores T-Cell Rejection Function in Tumors. Cancer Research. https://doi.org/10.1158/0008-5472.can-12-4100
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