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CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer
Abstract
Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, metabolic dysregulation, poor memory recall and homeostatic self-renewal, and distinct transcriptional and epigenetic programs. The ability to reinvigorate Tex cells through inhibitory receptor blockade, such as αPD-1, highlights the therapeutic potential of targeting this population. Emerging insights into the mechanisms of exhaustion are informing immunotherapies for cancer and chronic infections. However, like other immune cells, Tex cells are heterogeneous and include progenitor and terminal subsets with unique characteristics and responses to checkpoint blockade. Here, we review our current understanding of Tex cell biology, including the developmental paths, transcriptional and epigenetic features, and cell intrinsic and extrinsic factors contributing to exhaustion and how this knowledge may inform therapeutic targeting of Tex cells in chronic infections, autoimmunity, and cancer.
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Cancer immunotherapy using checkpoint blockade
Ribas, A., & Wolchok, J. D. (2018) · Science · doi:10.1126/science.aar4060 · Cited by 6,791
Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade
Le, D. T., Durham, J. N., Smith, K. N., Wang, H., Bartlett, B. R., Aulakh, L. K., Lu, S., Kemberling, H., Wilt, C., Luber, B. S., et al. (2017) · Science · doi:10.1126/science.aan6733 · Cited by 6,645
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
Tumor-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
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
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Wolchok, J. D., Kluger, H., Callahan, M. K., Postow, M. A., Rizvi, N. A., Lesokhin, A. M., Segal, N. H., Ariyan, C. E., Gordon, R.-A., Reed, K., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1302369 · Cited by 4,230
Wherry, E. J. (2011) · Nature Immunology · doi:10.1038/ni.2035 · Cited by 4,062
Self-citationMetabolic 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
Type I interferons in infectious disease
McNab, F., Mayer-Barber, K., Sher, A., Wack, A., & O'Garra, A. (2015) · Nature Reviews Immunology · doi:10.1038/nri3787 · Cited by 2,780
PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression
Day, C. L., Kaufmann, D. E., Kiepiela, P., Brown, J. A., Moodley, E. S., Reddy, S., Mackey, E. W., Miller, J. D., Leslie, A. J., DePierres, C., et al. (2006) · Nature · doi:10.1038/nature05115 · Cited by 2,680
Self-citation
Research works printed but not linked: 258
- 10.1016/S0065-2776(08)60525-8 · DOI · Paper page
- 10.1084/jem.127.2.307 · doi:10.1084/jem.127.2.307
- 10.1038/362758a0 · DOI · Paper page
- 10.1084/jem.187.9.1383 · DOI · Paper page
- 10.1111/j.1600-065X.2010.00926.x · DOI · Paper page
- 10.1016/j.immuni.2012.08.021 · DOI · Paper page
- 10.1016/j.it.2013.10.001 · DOI · Paper page
- 10.1084/jem.160.2.521 · DOI · Paper page
- Zinkernagel RM, 2002, Curr. Top. Microbiol. Immunol., 263, 1
- 10.1128/JVI.74.21.10249-10255.2000 · DOI · Paper page
- 10.1182/blood.V96.9.3094 · DOI · Paper page
- 10.1002/1521-4141(200103)31:3<677::AID-IMMU677>3.0.CO;2-M · DOI
- 10.1084/jem.191.9.1499 · DOI · Paper page
- 10.1128/JVI.75.12.5550-5558.2001 · DOI · Paper page
- 10.1038/cddis.2015.42 · DOI · Paper page
- 10.1038/ni1443 · DOI · Paper page
- 10.1016/j.it.2015.02.008 · DOI · Paper page
- 10.1158/1078-0432.CCR-15-1849 · DOI · Paper page
- 10.1182/blood-2008-09-179697 · DOI · Paper page
- 10.1038/9525 · DOI · Paper page
- 10.1084/jem.20100637 · DOI · Paper page
- 10.1073/pnas.1003345107 · DOI · Paper page
- 10.1038/cmi.2010.28 · DOI
- 10.1016/j.jim.2017.03.009 · DOI
- 10.1182/blood-2012-09-457531 · DOI · Paper page
- 10.1038/s41591-018-0010-1 · DOI · Paper page
- 10.1016/j.coi.2010.02.005 · DOI · Paper page
- 10.1172/JCI73639 · DOI · Paper page
- 10.1182/blood-2013-01-475939 · doi:10.1182/blood-2013-01-475939
- 10.4049/jimmunol.0803245 · DOI · Paper page
- 10.4049/jimmunol.167.9.5042 · DOI
- 10.1038/nature04444 · DOI · Paper page
- 10.1016/j.virol.2014.12.033 · DOI · Paper page
- 10.1073/pnas.252530499 · DOI · Paper page
- 10.1016/j.coi.2011.12.009 · DOI · Paper page
- Strome SE, 2003, Cancer Res, 63, 6501
- 10.1158/0008-5472.CAN-03-3259 · DOI · Paper page
- 10.1016/j.immuni.2014.01.005 · DOI · Paper page
- 10.1097/COH.0000000000000092 · DOI
- 10.3389/fimmu.2017.00760 · DOI · Paper page
- 10.1186/s12964-016-0160-z · DOI · Paper page
- 10.1073/pnas.0801497105 · DOI · Paper page
- 10.1084/jem.20061937 · DOI · Paper page
- 10.1126/science.1229620 · DOI · Paper page
- 10.4049/jimmunol.170.1.477 · DOI · Paper page
- 10.1128/JVI.77.8.4911-4927.2003 · DOI · Paper page
- 10.1073/pnas.0610335104 · DOI
- 10.1016/j.immuni.2009.06.019 · DOI · Paper page
- 10.4049/jimmunol.1000841 · DOI
- 10.4049/jimmunol.172.7.4204 · DOI
- 10.1038/ni.2046 · DOI · Paper page
- 10.1084/jem.186.7.1099 · doi:10.1084/jem.186.7.1099
- 10.1128/JVI.01579-09 · DOI
- 10.4049/jimmunol.168.7.3660 · DOI
- 10.1016/j.immuni.2009.11.007 · DOI · Paper page
- 10.1016/S1074-7613(00)80664-0 · DOI · Paper page
- 10.1073/pnas.0407192101 · DOI · Paper page
- 10.1128/JVI.02021-06 · DOI · Paper page
- 10.1007/s11904-014-0246-4 · DOI
- 10.4049/jimmunol.172.8.4875 · DOI · Paper page
- 10.1073/pnas.1604256113 · DOI
- 10.1038/nm.1953 · DOI · Paper page
- 10.1128/JVI.78.11.5535-5545.2004 · DOI · Paper page
- 10.1038/ni.2606 · DOI · Paper page
- 10.1128/JVI.01499-09 · DOI
- 10.4049/jimmunol.171.10.5372 · DOI
- 10.1038/ncomms15050 · DOI
- 10.1016/j.immuni.2016.07.021 · DOI · Paper page
- 10.1038/ni.1679 · DOI · Paper page
- 10.1038/ni1515 · DOI · Paper page
- 10.1128/JVI.01177-06 · DOI · Paper page
- 10.1016/j.jhep.2014.07.005 · DOI · Paper page
- 10.1038/nature07662 · DOI · Paper page
- 10.1016/j.immuni.2016.04.022 · DOI · Paper page
- 10.1084/jem.20151159 · DOI · Paper page
- 10.1016/j.it.2014.12.004 · DOI · Paper page
- 10.1016/j.immuni.2011.12.007 · DOI · Paper page
- 10.1126/scisignal.2002796 · DOI · Paper page
- 10.1128/MCB.25.21.9543-9553.2005 · DOI · Paper page
- 10.1038/ncomms7692 · DOI · Paper page
- 10.1016/j.immuni.2014.10.013 · DOI · Paper page
- 10.4049/jimmunol.172.8.4661 · DOI · Paper page
- 10.1016/j.celrep.2016.06.078 · DOI · Paper page
- 10.1084/jem.20151570 · DOI · Paper page
- 10.1016/j.cell.2015.08.052 · DOI · Paper page
- 10.1158/1535-7163.MCT-14-0400 · DOI
- 10.1016/j.jconrel.2017.02.034 · DOI
- 10.1038/cmi.2015.20 · doi:10.1038/cmi.2015.20
- 10.1016/j.molmed.2017.07.006 · DOI
- 10.1016/j.immuni.2016.10.028 · DOI · Paper page
- 10.1038/ni.3325 · DOI · Paper page
- 10.1038/nri.2017.51 · DOI
- 10.1111/j.0105-2896.2006.00382.x · DOI · Paper page
- Matloubian M, 1994, J. Virol., 68, 8056, 10.1128/jvi.68.12.8056-8063.1994 · DOI · Paper page
- 10.1073/pnas.0809818106 · DOI · Paper page
- 10.1084/jem.20150598 · DOI · Paper page
- 10.4049/jimmunol.0800997 · DOI · Paper page
- 10.1371/journal.pmed.0050100 · DOI · Paper page
- 10.1084/jem.20011723 · DOI
- 10.1007/s11904-008-0003-7 · DOI
- 10.1128/JVI.02844-06 · DOI · Paper page
- 10.1172/JCI26856 · DOI
- 10.1128/JVI.00889-12 · DOI · Paper page
- 10.4049/jimmunol.1403237 · DOI
- 10.1016/j.coi.2010.02.013 · DOI · Paper page
- 10.1038/nri2251 · DOI · Paper page
- 10.1016/j.immuni.2014.04.010 · DOI
- Wilson EB, 2011, Curr. Top. Microbiol. Immunol., 350, 39
- 10.1038/nm1492 · DOI · Paper page
- 10.1073/pnas.0811139106 · DOI
- 10.1038/nm.2106 · DOI · Paper page
- 10.4049/jimmunol.180.9.5771 · DOI · Paper page
- 10.1111/j.1365-2567.2010.03255.x · DOI · Paper page
- 10.1007/s00251-003-0594-5 · DOI · Paper page
- 10.1111/j.1572-0241.2002.05926.x · doi:10.1111/j.1572-0241.2002.05926.x
- 10.1073/pnas.97.26.14467 · DOI · Paper page
- 10.1084/jem.20061462 · DOI · Paper page
- 10.1016/j.cellimm.2014.12.012 · DOI
- 10.1038/nature02006 · DOI · Paper page
- 10.1146/annurev.immunol.24.021605.090737 · DOI · Paper page
- 10.1084/jem.20012076 · DOI · Paper page
- 10.1016/j.immuni.2009.06.015 · DOI · Paper page
- 10.1172/JCI115059 · doi:10.1172/jci115059
- 10.1046/j.1365-2893.1997.00124.x · DOI
- 10.1002/eji.200637023 · DOI
- 10.1038/nm866 · DOI · Paper page
- 10.1172/JCI67008 · DOI · Paper page
- 10.1517/14712598.6.12.1323 · DOI
- 10.1056/NEJMoa0903175 · DOI · Paper page
- 10.1002/cyto.1132 · DOI
- 10.1097/00002030-200401230-00010 · DOI
- 10.1126/science.1174182 · DOI · Paper page
- 10.1126/science.1172815 · DOI · Paper page
- 10.1126/science.1175194 · DOI · Paper page
- 10.1172/JCI81400 · DOI
- 10.1146/annurev.immunol.26.021607.090316 · DOI · Paper page
- 10.1084/jem.20101773 · DOI · Paper page
- 10.1016/j.it.2017.10.003 · DOI
- 10.1016/j.celrep.2015.09.069 · DOI
- 10.1038/ni.2834 · DOI · Paper page
- 10.1038/nm.2232 · DOI · Paper page
- 10.1182/blood.V99.9.3263 · DOI · Paper page
- 10.1038/nri3506 · DOI
- 10.1128/JVI.02516-10 · DOI
- 10.1006/cyto.1998.0484 · DOI
- 10.1126/sciimmunol.aai8593 · DOI · Paper page
- 10.1038/nature13554 · DOI · Paper page
- 10.1172/JCI90745 · DOI
- 10.1172/JCI89488 · DOI
- 10.4049/jimmunol.1101029 · DOI · Paper page
- 10.1016/S1471-4906(01)02154-8 · DOI · Paper page
- Linnemeyer PA, 1993, J. Immunol., 150, 3747, 10.4049/jimmunol.150.9.3747 · DOI
- 10.1038/nm.3831 · DOI · Paper page
- 10.1182/blood-2006-12-064527 · DOI · Paper page
- 10.4049/jimmunol.177.10.6780 · DOI · Paper page
- 10.4161/onci.26246 · DOI · Paper page
- 10.1371/journal.ppat.1005177 · DOI · Paper page
- 10.4049/jimmunol.1301158 · DOI · Paper page
- 10.1084/jem.20101956 · DOI · Paper page
- 10.1016/j.vaccine.2015.08.096 · DOI
- Teague TK, 1997, J. Immunol., 158, 5791, 10.4049/jimmunol.158.12.5791 · DOI · Paper page
- 10.4049/jimmunol.180.12.7958 · DOI
- 10.1038/ni.3436 · DOI
- 10.1158/0008-5472.CAN-11-1620 · DOI · Paper page
- 10.1016/j.immuni.2016.01.013 · DOI · Paper page
- 10.1016/j.bbrc.2009.04.134 · DOI
- 10.1111/imr.12085 · DOI · Paper page
- 10.1016/j.chom.2013.05.014 · DOI
- 10.1111/imr.12084 · DOI
- 10.1038/nature10624 · DOI · Paper page
- 10.1073/pnas.1320999110 · DOI
- 10.1073/pnas.0702257104 · DOI · Paper page
- 10.1016/j.cell.2009.06.036 · DOI · Paper page
- 10.4049/jimmunol.1100038 · DOI
- 10.1073/pnas.192461099 · DOI · Paper page
- 10.1002/eji.200324228 · DOI · Paper page
- 10.4049/jimmunol.173.2.945 · DOI · Paper page
- 10.1016/j.febslet.2004.07.083 · DOI · Paper page
- 10.1016/j.celrep.2018.03.026 · DOI · Paper page
- 10.1084/jem.20142237 · DOI · Paper page
- 10.1084/jem.20121015 · DOI
- 10.1016/j.ccell.2015.03.001 · DOI · Paper page
- 10.1001/jamaoncol.2015.3934 · DOI
- 10.1073/pnas.0915174107 · DOI · Paper page
- 10.1016/j.it.2018.04.005 · DOI
- 10.1002/eji.201344413 · DOI
- 10.1016/j.ccell.2014.10.018 · DOI · Paper page
- 10.1038/ni.1674 · DOI · Paper page
- 10.1172/JCI80445 · DOI · Paper page
- 10.1093/intimm/dxp107 · DOI
- 10.1038/nri2366 · DOI
- 10.1073/pnas.1009731107 · DOI · Paper page
- 10.1038/nature19330 · DOI · Paper page
- 10.1371/journal.pone.0003454 · DOI
- 10.1128/JVI.00639-09 · DOI · Paper page
- 10.1084/jem.20081398 · DOI · Paper page
- 10.1172/JCI43127 · DOI · Paper page
- 10.1371/journal.pone.0047648 · DOI · Paper page
- 10.1002/eji.201141852 · DOI
- 10.1038/nri2526 · DOI · Paper page
200 of 258 shown
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Metadata
- Authors
- McLane, L. M., Abdel-Hakeem, M. S., & Wherry, E. J.
- Venue
- Annual Review of Immunology
- Publisher
- Annual Reviews
- Published
- 2019-04-26
- Volume
- 37
- Issue
- 1
- Pages
- 457-495
- ISSN
- 0732-0582 (ISSN-L)
- 1545-3278
- OpenAlex
- W2912648593
- Cited by
- 1,975
- References
- 52
- FWCI
- 23.11
- Type
- journal article
- Language
- en
- Open access
- closed
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