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Cdk5 disruption attenuates tumor PD-L1 expression and promotes antitumor immunity
Open accessAbstract
Cyclin suppresses antitumor immunity: Despite the dramatic success of cancer immunotherapy, many types of cancer do not respond. Understanding why could help us to find ways to enhance the overall responsiveness of tumors to immunotherapies. Dorand et al. report that cyclin-dependent kinase 5 (Cdk5), an enzyme that is highly expressed by neurons in many brain cancers, may dampen the ability of T cells to reject tumors. In a mouse model of medulloblastoma, if tumors were Cdk5 deficient, T cells were able to remove them. This heightened antitumor immunity correlated with reduced expression of the inhibitory molecule programmed cell death ligand 1 (PD-L1), a target of current cancer immunotherapies. Science , this issue p. 399
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Cites
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838
Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer
Twyman-Saint Victor, C., Rech, A. J., Maity, A., Rengan, R., Pauken, K. E., Stelekati, E., Benci, J. L., Xu, B., Dada, H., Odorizzi, P. M., et al. (2015) · Nature · doi:10.1038/nature14292 · Cited by 2,434
Inhibitory B7-family molecules in the tumour microenvironment
Zou, W., & Chen, L. (2008) · Nature Reviews Immunology · doi:10.1038/nri2326 · Cited by 1,608
MYC regulates the antitumor immune response through CD47 and PD-L1
Casey, S. C., Tong, L., Li, Y., Do, R., Walz, S., Fitzgerald, K. N., Gouw, A. M., Baylot, V., Gütgemann, I., Eilers, M., et al. (2016) · Science · doi:10.1126/science.aac9935 · Cited by 1,403
Cited by
Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy
Sharma, P., Hu-Lieskovan, S., Wargo, J. A., & Ribas, A. (2017) · Cell · doi:10.1016/j.cell.2017.01.017 · Cited by 5,588
Cyclin D–CDK4 kinase destabilizes PD-L1 via cullin 3–SPOP to control cancer immune surveillance
Zhang, J., Bu, X., Wang, H., Zhu, Y., Geng, Y., Nihira, N. T., Tan, Y., Ci, Y., Wu, F., Dai, X., et al. (2018) · Nature · doi:10.1038/nature25015 · Cited by 1,013
Identification of CMTM6 and CMTM4 as PD-L1 protein regulators
Mezzadra, R., Sun, C., Jae, L. T., Gomez-Eerland, R., de Vries, E., Wu, W., Logtenberg, M. E. W., Slagter, M., Rozeman, E. A., Hofland, I., et al. (2017) · Nature · doi:10.1038/nature23669 · Cited by 697
Mechanisms regulating PD-L1 expression on tumor and immune cells
Chen, S., Crabill, G. A., Pritchard, T. S., McMiller, T. L., Wei, P., Pardoll, D. M., Pan, F., & Topalian, S. L. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0770-2 · Cited by 459
Aerobic glycolysis promotes tumor immune evasion by hexokinase2-mediated phosphorylation of IκBα
Guo, D., Tong, Y., Jiang, X., Meng, Y., Jiang, H., Du, L., Wu, Q., Li, S., Luo, S., Li, M., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.08.002 · Cited by 423
Metadata
- Authors
- Dorand, R. D., Nthale, J., Myers, J. T., Barkauskas, D. S., Avril, S., Chirieleison, S. M., Pareek, T. K., Abbott, D. W., Stearns, D. S., Letterio, J. J., Huang, A. Y., & Petrosiute, A.
- Venue
- Science
- Published
- 2016-07-22
- Volume
- 353
- Issue
- 6297
- Pages
- 399-403
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2502908858
- Cited by
- 315
- References
- 4
- FWCI
- 17.93
- Type
- journal article
- Language
- en
- Open access
- green
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- Dorand, R. D., Nthale, J., Myers, J. T., Barkauskas, D. S., Avril, S., Chirieleison, S. M., Pareek, T. K., Abbott, D. W., Stearns, D. S., Letterio, J. J., Huang, A. Y., & Petrosiute, A. (2016). Cdk5 disruption attenuates tumor PD-L1 expression and promotes antitumor immunity. Science. https://doi.org/10.1126/science.aae0477
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