The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Intratumoral IL-12 combined with CTLA-4 blockade elicits T cell–mediated glioma rejection
Open accessAbstract
Glioblastomas (GBs) are the most aggressive form of primary brain cancer and virtually incurable. Accumulation of regulatory T (T reg) cells in GBs is thought to contribute to the dampening of antitumor immunity. Using a syngeneic mouse model for GB, we tested whether local delivery of cytokines could render the immunosuppressive GB microenvironment conducive to an antitumor immune response. IL-12 but not IL-23 reversed GB-induced immunosuppression and led to tumor clearance. In contrast to models of skin or lung cancer, IL-12–mediated glioma rejection was T cell dependent and elicited potent immunological memory. To translate these findings into a clinically relevant setting, we allowed for GB progression before initiating therapy. Combined intratumoral IL-12 application with systemic blockade of the co-inhibitory receptor CTLA-4 on T cells led to tumor eradication even at advanced disease stages where monotherapy with either IL-12 or CTLA-4 blockade failed. The combination of IL-12 and CTLA-4 blockade acts predominantly on CD4+ cells, causing a drastic decrease in FoxP3+ T reg cells and an increase in effector T (T eff) cells. Our data provide compelling preclinical findings warranting swift translation into clinical trials in GB and represent a promising approach to increase response rates of CTLA-4 blockade in solid tumors.
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Simpson, T. R., Li, F., Montalvo-Ortiz, W., Sepulveda, M. A., Bergerhoff, K., Arce, F., Roddie, C., Henry, J. Y., Yagita, H., Wolchok, J. D., et al. (2013) · Journal of Experimental Medicine · doi:10.1084/jem.20130579 · Cited by 1,472
IL-23 promotes tumour incidence and growth
Langowski, J. L., Zhang, X., Wu, L., Mattson, J. D., Chen, T., Smith, K., Basham, B., McClanahan, T., Kastelein, R. A., & Oft, M. (2006) · Nature · doi:10.1038/nature04808 · Cited by 1,018
Selby, M. J., Engelhardt, J. J., Quigley, M., Henning, K. A., Chen, T., Srinivasan, M., & Korman, A. J. (2013) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-13-0013 · Cited by 857
Cited by
Turning Cold into Hot: Firing up the Tumor Microenvironment
Duan, Q., Zhang, H., Zheng, J., & Zhang, L. (2020) · Trends in Cancer · doi:10.1016/j.trecan.2020.02.022 · Cited by 934
Teng, M. W. L., Bowman, E. P., McElwee, J. J., Smyth, M. J., Casanova, J.-L., Cooper, A. M., & Cua, D. J. (2015) · Nature Medicine · doi:10.1038/nm.3895 · Cited by 873
Two FOXP3+CD4+ T cell subpopulations distinctly control the prognosis of colorectal cancers
Saito, T., Nishikawa, H., Wada, H., Nagano, Y., Sugiyama, D., Atarashi, K., Maeda, Y., Hamaguchi, M., Ohkura, N., Sato, E., et al. (2016) · Nature Medicine · doi:10.1038/nm.4086 · Cited by 871
Reardon, D. A., Gokhale, P. C., Klein, S. R., Ligon, K. L., Rodig, S. J., Ramkissoon, S. H., Jones, K. L., Conway, A. S., Liao, X., Zhou, J., et al. (2016) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-15-0151 · Cited by 405
Brain Tumor Microenvironment and Host State: Implications for Immunotherapy
Tomaszewski, W., Sanchez-Perez, L., Gajewski, T. F., & Sampson, J. H. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-1627 · Cited by 319
Metadata
- Authors
- vom Berg, J., Vrohlings, M., Haller, S., Haimovici, A., Kulig, P., Sledzinska, A., Weller, M., & Becher, B.
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2013-11-25
- Volume
- 210
- Issue
- 13
- Pages
- 2803-2811
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2152283027
- Cited by
- 213
- References
- 3
- FWCI
- 9.64
- Type
- journal article
- Language
- en
- Open access
- bronze
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- vom Berg, J., Vrohlings, M., Haller, S., Haimovici, A., Kulig, P., Sledzinska, A., Weller, M., & Becher, B. (2013). Intratumoral IL-12 combined with CTLA-4 blockade elicits T cell–mediated glioma rejection. Journal of Experimental Medicine. https://doi.org/10.1084/jem.20130678
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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