Cited by 4,652T-cell and B-cell ImmunologyCancer Immunotherapy and BiomarkersImmune Cell Function and Interaction

The DOI matches its Crossref record; 155 of the 156 references it cites were found in a registry or an index.

Molecular and cellular insights into T cell exhaustion

Open access

Wherry, E. John, Kurachi, Makoto·2015·Nature Reviews Immunology

Open this paper in CoChat — free account

Abstract

In chronic infections and cancer, T cells are exposed to persistent antigen and/or inflammatory signals. This scenario is often associated with the deterioration of T cell function: a state called 'exhaustion'. Exhausted T cells lose robust effector functions, express multiple inhibitory receptors and are defined by an altered transcriptional programme. T cell exhaustion is often associated with inefficient control of persisting infections and tumours, but revitalization of exhausted T cells can reinvigorate immunity. Here, we review recent advances that provide a clearer molecular understanding of T cell exhaustion and reveal new therapeutic targets for persisting infections and cancer.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1038/nri3862

Cites

155 of 155 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay‐Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,320
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838
Nivolumab plus Ipilimumab in Advanced Melanoma
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
T cell exhaustion
Wherry, E. J. (2011) · Nature Immunology · doi:10.1038/ni.2035 · Cited by 4,062
Self-citation
Restoring function in exhausted CD8 T cells during chronic viral infection
Barber, D. L., Wherry, E. J., Masopust, D., Zhu, B., Allison, J. P., Sharpe, A. H., Freeman, G. J., & Ahmed, R. (2005) · Nature · doi:10.1038/nature04444 · Cited by 4,057
Self-citation
Regulation of type I interferon responses
Ivashkiv, L. B., & Donlin, L. T. (2013) · Nature reviews. Immunology · doi:10.1038/nri3581 · Cited by 3,442
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
Control of Viremia in Simian Immunodeficiency Virus Infection by CD8 + Lymphocytes
Schmitz, J. E., Kuroda, M. J., Santra, S., Sasseville, V. G., Simon, M. A., Lifton, M. A., Rácz, P., Tenner‐Racz, K., Dalesandro, M. R., Scallon, B. J., et al. (1999) · Science · doi:10.1126/science.283.5403.857 · Cited by 2,167
Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
Wherry, E. J., Ha, S.-J., Kaech, S. M., Haining, W. N., Sarkar, S., Kalia, V., Subramaniam, S., Blattman, J. N., Barber, D. L., & Ahmed, R. (2007) · Immunity · doi:10.1016/j.immuni.2007.09.006 · Cited by 2,103
Self-citation

Show all 156 references

Sorted by citations

Items 301–400 of 1,019

Blocking type I interferon signaling enhances T cell recovery and reduces HIV-1 reservoirs
Cheng, L., Ma, J., Li, J., Li, D., Li, G., Li, F., Zhang, Q., Yu, H., Yasui, F., Ye, C., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci90745 · Cited by 179
CRISPR–Cas: a tool for cancer research and therapeutics
Yin, H., Xue, W., & Anderson, D. G. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0166-8 · Cited by 185
Trisomy 21 dysregulates T cell lineages toward an autoimmunity-prone state associated with interferon hyperactivity
Araya, P., Waugh, K. A., Sullivan, K. D., Núñez, N. G., Roselli, E., Smith, K. P., Granrath, R. E., Rachubinski, A. L., Enriquez Estrada, B., Butcher, E. T., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1908129116 · Cited by 179
Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19
Unterman, A., Sumida, T. S., Nouri, N., Yan, X., Zhao, A., Gasque, V., Schupp, J. C., Asashima, H., Liu, Y., Cosme, C., et al. (2022) · Nature Communications · doi:10.1038/s41467-021-27716-4 · Cited by 181
SALL4-mediated upregulation of exosomal miR-146a-5p drives T-cell exhaustion by M2 tumor-associated macrophages in HCC
Yin, C., Han, Q., Xu, D., Zheng, B., Zhao, X., & Zhang, J. (2019) · OncoImmunology · doi:10.1080/2162402x.2019.1601479 · Cited by 182
Development of immune checkpoint therapy for cancer
Fritz, J. M., & Lenardo, M. J. (2019) · The Journal of Experimental Medicine · doi:10.1084/jem.20182395 · Cited by 179
Depletion of BATF in CAR-T cells enhances antitumor activity by inducing resistance against exhaustion and formation of central memory cells
Zhang, X., Zhang, C., Qiao, M., Cheng, C., Tang, N., Lu, S., Sun, W. C., Xu, B., Cao, Y., Wei, X., et al. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.09.013 · Cited by 176
CD155 on Tumor Cells Drives Resistance to Immunotherapy by Inducing the Degradation of the Activating Receptor CD226 in CD8+ T Cells
Braun, M., Aguilera, A. R., Sundarrajan, A., Corvino, D., Stannard, K. A., Krumeich, S., Das, I., Lima, L. G., Guzman, L. G. M., Li, K., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.09.010 · Cited by 176
Radiotherapy remodels the tumor microenvironment for enhancing immunotherapeutic sensitivity
Liu, S., Wang, W., Hu, S., Jia, B., Tuo, B., Sun, H., Wang, Q., Liu, Y., & Sun, Z. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-06211-2 · Cited by 194
Approved CAR T cell therapies: ice bucket challenges on glaring safety risks and long-term impacts
Zheng, P., Kros, J. M., & Li, J. (2018) · Drug Discovery Today · doi:10.1016/j.drudis.2018.02.012 · Cited by 178
Macrophage-Derived Granulin Drives Resistance to Immune Checkpoint Inhibition in Metastatic Pancreatic Cancer
Quaranta, V., Rainer, C., Nielsen, S. R., Raymant, M., Ahmed, M. S., Engle, D. D., Taylor, A., Murray, T., Campbell, F., Palmer, D. H., et al. (2018) · Cancer Research · doi:10.1158/0008-5472.can-17-3876 · Cited by 171
Myeloma escape after stem cell transplantation is a consequence of T-cell exhaustion and is prevented by TIGIT blockade
Minnie, S. A., Kuns, R. D., Gartlan, K. H., Zhang, P., Wilkinson, A., Samson, L. D., Guillerey, C., Engwerda, C. R., MacDonald, K. P. A., Smyth, M. J., et al. (2018) · Blood · doi:10.1182/blood-2018-01-825240 · Cited by 171
Counteracting CAR T cell dysfunction
Poorebrahim, M., Melief, J., de Coaña, Y. P., Wickström, S. L., Arregui, A. C., & Kiessling, R. W. (2020) · Oncogene · doi:10.1038/s41388-020-01501-x · Cited by 172
Autoreactive CD8+ T cell exhaustion distinguishes subjects with slow type 1 diabetes progression
Wiedeman, A. E., Muir, V. S., Rosasco, M. G., DeBerg, H. A., Presnell, S., Haas, B., Dufort, M. J., Speake, C., Greenbaum, C. J., Serti, E., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci126595 · Cited by 168
Combining STING-based neoantigen-targeted vaccine with checkpoint modulators enhances antitumor immunity in murine pancreatic cancer
Kinkead, H. L., Hopkins, A. C., Lutz, E. R., Wu, A. A., Yarchoan, M. M., Cruz, K. A., Woolman, S., Vithayathil, T., Glickman, L. H., Ndubaku, C. O., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.122857 · Cited by 169
Chimeric STAR receptors using TCR machinery mediate robust responses against solid tumors
Liu, Y., Liu, G., Wang, J., Zheng, Z., Jia, L., Rui, W., Huang, D., Zhou, Z., Zhou, L., Wu, X., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abb5191 · Cited by 178
Targeting Immune Cell Checkpoints during Sepsis
Patil, N. K., Guo, Y., Luan, L., & Sherwood, E. R. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18112413 · Cited by 174
Low-Dose IFNγ Induces Tumor Cell Stemness in Tumor Microenvironment of Non–Small Cell Lung Cancer
Song, M., Yü, P., Zhang, K., Yang, L., Li, F., Zhang, C., Cheng, S., Yue, D., Maimela, N. R., Qu, J., et al. (2019) · Cancer Research · doi:10.1158/0008-5472.can-19-0596 · Cited by 179
Immune Deregulation in Sepsis and Septic Shock: Reversing Immune Paralysis by Targeting PD-1/PD-L1 Pathway
Nakamori, Y., Park, E. J., & Shimaoka, M. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.624279 · Cited by 176
Nonreversible MAIT cell‐dysfunction in chronic hepatitis C virus infection despite successful interferon‐free therapy
Hengst, J., Strunz, B., Deterding, K., Ljunggren, H., Leeansyah, E., Manns, M. P., Cornberg, M., Sandberg, J. K., Wedemeyer, H. H., & Björkström, N. K. (2016) · European Journal of Immunology · doi:10.1002/eji.201646447 · Cited by 166
Malaria-induced interferon-γ drives the expansion of Tbethi atypical memory B cells
Obeng-Adjei, N., Portugal, S., Holla, P., Li, S., Sohn, H., Ambegaonkar, A. A., Skinner, J., Bowyer, G., Doumbo, O. K., Traoré, B., et al. (2017) · PLoS Pathogens · doi:10.1371/journal.ppat.1006576 · Cited by 163
Type I interferon signaling, regulation and gene stimulation in chronic virus infection
Lukhele, S., Boukhaled, G. M., & Brooks, D. G. (2019) · Seminars in Immunology · doi:10.1016/j.smim.2019.05.001 · Cited by 173
Leukocyte heterogeneity in pancreatic ductal adenocarcinoma: phenotypic and spatial features associated with clinical outcome
Liudahl, S. M., Betts, C. B., Sivagnanam, S., Morales-Oyarvide, V., da Silva, A., Yuan, C., Hwang, S., Grossblatt-Wait, A., Leis, K. R., Larson, W., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0841 · Cited by 164
Critical challenges and emerging opportunities in hepatitis C virus research in an era of potent antiviral therapy: Considerations for scientists and funding agencies
Bartenschlager, R. F. W., Baumert, T. F., Bukh, J., Houghton, M., Lemon, S. M., Lindenbach, B. D., Lohmann, V., Moradpour, D., Pietschmann, T., Rice, C. M., et al. (2018) · Virus Research · doi:10.1016/j.virusres.2018.02.016 · Cited by 163
Mass cytometry of Hodgkin lymphoma reveals a CD4+ regulatory T-cell–rich and exhausted T-effector microenvironment
Cader, F. Z., Schackmann, R. C. J., Hu, X. S., Wienand, K., Redd, R. A., Chapuy, B., Ouyang, J., Paul, N. E., Gjini, E., Lipschitz, M., et al. (2018) · Blood · doi:10.1182/blood-2018-04-843714 · Cited by 166
Cellular and gene signatures of tumor-infiltrating dendritic cells and natural-killer cells predict prognosis of neuroblastoma
Melaiu, O., Chierici, M., Lucarini, V., Jurman, G., Conti, L. A., Vito, R. D., Boldrini, R., Cifaldi, L., Castellano, A., Furlanello, C., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19781-y · Cited by 164
Immunomodulatory Effects of Lenvatinib Plus Anti–Programmed Cell Death Protein 1 in Mice and Rationale for Patient Enrichment in Hepatocellular Carcinoma
Torrens, L., Montironi, C., Puigvehí, M., Mesropian, A., Leslie, J., Haber, P. K., Maeda, M., Balaseviciute, U., Willoughby, C. E., Abril‐Fornaguera, J., et al. (2021) · Hepatology · doi:10.1002/hep.32023 · Cited by 161
Immunotherapy: A promising approach to reverse sepsis-induced immunosuppression
Patil, N. K., Bohannon, J. K., & Sherwood, E. R. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2016.07.019 · Cited by 173
B‐cell responses to HIV infection
Moir, S. L., & Fauci, A. S. (2017) · Immunological Reviews · doi:10.1111/imr.12502 · Cited by 171
Memory-like HCV-specific CD8+ T cells retain a molecular scar after cure of chronic HCV infection
Hensel, N., Gu, Z., Sagar, Wieland, D., Jechow, K., Kemming, J. S., Llewellyn‐Lacey, S., Emma Gostick, D., Sogukpinar, O., Emmerich, F., et al. (2021) · Nature Immunology · doi:10.1038/s41590-020-00817-w · Cited by 159
The transcription factor Runx3 guards cytotoxic CD8+ effector T cells against deviation towards follicular helper T cell lineage
Shan, Q., Zeng, Z., Xing, S., Li, F., Hartwig, S. M., Gullicksrud, J. A., Kurup, S. P., Budimir, N., Yao, S., Martin, M. D., et al. (2017) · Nature Immunology · doi:10.1038/ni.3773 · Cited by 160
Tumor-associated B cells and humoral immune response in head and neck squamous cell carcinoma
Lechner, A., Schlößer, H., Thelen, M., Wennhold, K., Rothschild, S. I., Gilles, R., Quaas, A., Siefer, O. G., Huebbers, C. U., Cukuroglu, E., et al. (2019) · OncoImmunology · doi:10.1080/2162402x.2018.1535293 · Cited by 160
Immune cell constitution in the tumor microenvironment predicts the outcome in diffuse large B-cell lymphoma
Autio, M. I., Leivonen, S., Brück, O. E., Mustjoki, S. M., Jørgensen, J. M., Karjalainen‐Lindsberg, M., Beiske, K., Holte, H., Pellinen, T. S., & Leppä, S. (2020) · Haematologica · doi:10.3324/haematol.2019.243626 · Cited by 163
Microenvironmental IL-6 inhibits anti-cancer immune responses generated by cytotoxic chemotherapy
Bent, E. H., Millán-Barea, L. R., Zhuang, I., Goulet, D. R., Fröse, J., & Hemann, M. T. (2021) · Nature Communications · doi:10.1038/s41467-021-26407-4 · Cited by 167
Metformin Enhances the Antitumor Activity of CD8+ T Lymphocytes via the AMPK–miR-107–Eomes–PD-1 Pathway
Zhang, Z., Li, F., Tian, Y., Cao, L., Gao, Q., Zhang, C., Zhang, K., Shen, C., Ping, Y., Maimela, N. R., et al. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.1901213 · Cited by 162
Targeting Metabolism in Cancer Cells and the Tumour Microenvironment for Cancer Therapy
Li, J., Eu, J. Q., Kong, L. R., Wang, L., Lim, Y. C., Goh, B. C., & Wong, A. L. (2020) · Molecules · doi:10.3390/molecules25204831 · Cited by 165
Engineered erythrocytes covalently linked to antigenic peptides can protect against autoimmune disease
Pishesha, N., Bilate, A. M. B., Wibowo, M. C., Huang, N.-J., Li, Z., Deshycka, R., Bousbaine, D., Li, H., Patterson, H. C., Dougan, S. K., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1701746114 · Cited by 158
Immune Checkpoints in Circulating and Tumor-Infiltrating CD4+ T Cell Subsets in Colorectal Cancer Patients
Toor, S. M., Murshed, K., Al‐Dhaheri, M., Khawar, M., Nada, M. A., & Elkord, E. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02936 · Cited by 161
Single-cell transcriptome analysis reveals TOX as a promoting factor for T cell exhaustion and a predictor for anti-PD-1 responses in human cancer
Kim, K.-S., Park, S., Park, S. Y., Kim, G., Park, S. M., Cho, J.-W., Kim, D., Park, Y. M., Koh, Y. W., Kim, H. R., et al. (2020) · Genome Medicine · doi:10.1186/s13073-020-00722-9 · Cited by 164
Mechanisms of T-Cell Exhaustion in Pancreatic Cancer
Saka, D., Gökalp, M., Piyade, B., Çevik, N. C., Sever, E. A., Unutmaz, D., Ceyhan, G. O., Demir, İ. E., & Asimgil, H. (2020) · Cancers · doi:10.3390/cancers12082274 · Cited by 160
The Single-Cell Immunogenomic Landscape of B and Plasma Cells in Early-Stage Lung Adenocarcinoma
Hao, D., Han, G., Sinjab, A. F., Gomez-Bolanos, L. I., Lazcano, R., Serrano, A. G., Hernandez, S. D., Dai, E., Cao, X., Hu, J., et al. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-1658 · Cited by 161
In-depth virological and immunological characterization of HIV-1 cure after CCR5Δ32/Δ32 allogeneic hematopoietic stem cell transplantation
Jensen, B.-E. O., Knops, E., Cords, L., Lübke, N., Salgado, M., Busman-Sahay, K., Estes, J. D., Huyveneers, L. E. P., Perdomo-Celis, F., Wittner, M., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02213-x · Cited by 158
Elevated Exhaustion Levels of NK and CD8+ T Cells as Indicators for Progression and Prognosis of COVID-19 Disease
Li, M., Guo, W., Dong, Y., Wang, X., Dai, D., Liu, X., Wu, Y., Li, M., Zhang, W., Zhou, H., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.580237 · Cited by 157
Disease tolerance: concept and mechanisms
McCarville, J. L., & Ayres, J. S. (2017) · Current Opinion in Immunology · doi:10.1016/j.coi.2017.12.003 · Cited by 154
TCRαβ + CD3 + CD4 − CD8 − (double negative) T cells in autoimmunity
Brandt, D., & Hedrich, C. M. (2018) · Autoimmunity Reviews · doi:10.1016/j.autrev.2018.02.001 · Cited by 166
Mitochondria: the indispensable players in innate immunity and guardians of the inflammatory response
Mohanty, A., Tiwari-Pandey, R., & Pandey, N. R. (2019) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-019-00507-9 · Cited by 164
The role of lncRNAs and circRNAs in the PD-1/PD-L1 pathway in cancer immunotherapy
Jiang, W., Pan, S., Chen, X., Wang, Z. P., & Zhu, X. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01406-7 · Cited by 162
Complete blood count alterations in COVID-19 patients
Palladino, M. (2021) · Biochemia Medica · doi:10.11613/bm.2021.030501 · Cited by 162
TAM receptor tyrosine kinases as emerging targets of innate immune checkpoint blockade for cancer therapy
Akalu, Y. T., Rothlin, C. V., & Ghosh, S. (2017) · Immunological Reviews · doi:10.1111/imr.12522 · Cited by 158
Trial watch: Peptide-based vaccines in anticancer therapy
Bezu, L., Kepp, O., Cerrato, G., Pol, J. G., Fucikova, J. P., Špíšek, R., Zitvogel, L., Kroemer, G., & Galluzzi, L. (2018) · OncoImmunology · doi:10.1080/2162402x.2018.1511506 · Cited by 158
Disease Tolerance as an Inherent Component of Immunity
Martins, R., Carlos, A. R., Braza, F., Thompson, J. A., Bastos-Amador, P., Ramos, S., & Soares, M. P. (2019) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042718-041739 · Cited by 151
CD8+ T cell exhaustion and cancer immunotherapy
Wang, Q., Qin, Y., & Li, B. (2023) · Cancer Letters · doi:10.1016/j.canlet.2022.216043 · Cited by 155
Engineering Polymer Hydrogel Nanoparticles for Lymph Node‐Targeted Delivery
Koker, S. D., Cui, J., Vanparijs, N., Albertazzi, L., Grooten, J., Caruso, F., & Geest, B. G. D. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201508626 · Cited by 154
Long non-coding RNA Lnc-Tim3 exacerbates CD8 T cell exhaustion via binding to Tim-3 and inducing nuclear translocation of Bat3 in HCC
Ji, J., Yin, Y., Ju, H., Xu, X., Liu, W., Fu, Q., Hu, J., Zhang, X., & Sun, B. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0528-7 · Cited by 156
CAR T Cell Therapy for Neuroblastoma
Richards, R. M., Sotillo, E., & Majzner, R. G. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02380 · Cited by 159
Understanding the mechanisms of resistance to CAR T-cell therapy in malignancies.
Cheng, J., Zhao, L., Zhang, Y., Qin, Y., Guan, Y., Zhang, T., Liu, C., & Zhou, J. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.01237 · Cited by 153
CAR-T Cells and Oncolytic Viruses: Joining Forces to Overcome the Solid Tumor Challenge
Guedan, S., & Alemany, R. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02460 · Cited by 158
The potential of activator protein 1 (AP-1) in cancer targeted therapy
Song, D., Lian, Y., & Zhang, L. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1224892 · Cited by 153
Overcoming Hypoxia-Mediated Tumor Progression: Combinatorial Approaches Targeting pH Regulation, Angiogenesis and Immune Dysfunction
McDonald, P. C., Chafe, S. C., & Dedhar, S. (2016) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2016.00027 · Cited by 154
Cytomegalovirus: Shape-Shifting the Immune System
Picarda, G. G. A., & Benedict, C. A. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1800171 · Cited by 152
Restoring, releasing or replacing adaptive immunity in chronic hepatitis B
Maini, M. K., & Burton, A. R. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0196-9 · Cited by 157
A Transcriptomic Method to Determine Airway Immune Dysfunction in T2-High and T2-Low Asthma
Peters, M. C., Ringel, L., Dyjack, N., Herrin, R., Woodruff, P. G., Rios, C., O’Connor, B., Fahy, J. V., & Seibold, M. A. (2019) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201807-1291oc · Cited by 151
Neuropilin-1 is a T cell memory checkpoint limiting long-term antitumor immunity
Liu, C., Somasundaram, A., Manne, S., Gocher, A. M., Szymczak-Workman, A. L., Vignali, K. M., Scott, E. N., Normolle, D. P., John Wherry, E., Lipson, E. J., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0733-2 · Cited by 151
Self-citation
The Emerging Role of CD244 Signaling in Immune Cells of the Tumor Microenvironment
Agresta, L., Hoebe, K. H. N., & Janssen, E. M. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02809 · Cited by 157
A combinational chemo-immune therapy using an enzyme-sensitive nanoplatform for dual-drug delivery to specific sites by cascade targeting
He, Y., Lei, L., Cao, J., Yang, X., Cai, S., Tong, F., Huang, D., Mei, H., Luo, K., Gao, H., et al. (2021) · Science Advances · doi:10.1126/sciadv.aba0776 · Cited by 148
Exploring Markers of Exhausted CD8 T Cells to Predict Response to Immune Checkpoint Inhibitor Therapy for Hepatocellular Carcinoma
Hsu, C., Ou, D., Bai, L., Chen, C., Lin, L., Huang, S.-F. K., Cheng, A., Jeng, Y., & Hsu, C. (2021) · Liver Cancer · doi:10.1159/000515305 · Cited by 151
Kidney-infiltrating T cells in murine lupus nephritis are metabolically and functionally exhausted
Tilstra, J. S., Avery, L., Menk, A. V., Gordon, R. A., Smita, S., Kane, L. P., Chikina, M., Delgoffe, G. M., & Shlomchik, M. J. (2018) · Journal of Clinical Investigation · doi:10.1172/jci120859 · Cited by 149
Novel Immune-Related Gene Signature for Risk Stratification and Prognosis of Survival in Lower-Grade Glioma
Zhang, M., Wang, X., Chen, X., Zhang, Q., & Hong, J. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.00363 · Cited by 145
T Cell Metabolism in Infection
Wik, J. A., & Skålhegg, B. S. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.840610 · Cited by 158
T-cell exhaustion signatures characterize the immune landscape and predict HCC prognosis via integrating single-cell RNA-seq and bulk RNA-sequencing
Chi, H., Zhao, S., Yang, J., Gao, X., Peng, G., Zhang, J., Xie, X., Song, G., Xu, K., Xia, Z., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1137025 · Cited by 153
IL-21 and T Cell Differentiation: Consider the Context
Tian, Y., & Zajac, A. J. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.06.001 · Cited by 152
EGFR-Mutated Non-Small Cell Lung Cancer and Resistance to Immunotherapy: Role of the Tumor Microenvironment
Madeddu, C., Donisi, C., Liscia, N., Lai, E., Scartozzi, M., & Macciò, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23126489 · Cited by 161
Immunosenescence: signaling pathways, diseases and therapeutic targets
Fu, Y., Wang, B., Alu, A., Hong, W., Hong, L., He, X., Shi, H., Cheng, P., & Yang, X. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02371-z · Cited by 168
Neuropilin-1: a checkpoint target with unique implications for cancer immunology and immunotherapy
Chuckran, C. A., Liu, C., Bruno, T. C., Workman, C. J., & Vignali, D. A. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-000967 · Cited by 147
Subclone-specific microenvironmental impact and drug response in refractory multiple myeloma revealed by single‐cell transcriptomics
Tirier, S. M., Mallm, J., Steiger, S., Poos, A. M., Awwad, M. H. S., Giesen, N., Casiraghi, N. A., Sušak, H., Bauer, K., Baumann, A., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26951-z · Cited by 148
Primary and acquired resistance to PD-1/PD-L1 blockade in cancer treatment
Wang, Q., & Wu, X. (2017) · International Immunopharmacology · doi:10.1016/j.intimp.2017.03.015 · Cited by 146
Soluble immune checkpoint-related proteins as predictors of tumor recurrence, survival, and T cell phenotypes in clear cell renal cell carcinoma patients
Wang, Q., Zhang, J., Tu, H., Liang, D., Chang, D. W., Ye, Y., & Wu, X. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0810-y · Cited by 146
Telomere Dynamics in Immune Senescence and Exhaustion Triggered by Chronic Viral Infection
Bellon, M., & Nicot, C. (2017) · Viruses · doi:10.3390/v9100289 · Cited by 147
Minimal PD-1 expression in mouse and human NK cells under diverse conditions
Judge, S. J., Dunai, C., Aguilar, E. G., Vick, S. C., Sturgill, I. R., Khuat, L. T., Stoffel, K. M., Dyke, J. V., Longo, D. L., Darrow, M. A., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci133353 · Cited by 147
A peripheral immune signature of responsiveness to PD-1 blockade in patients with classical Hodgkin lymphoma
Cader, F. Z., Hu, X. S., Goh, W. L., Wienand, K., Ouyang, J., Mandato, E., Redd, R. A., Lawton, L. N., Chen, P.-H., Weirather, J. L., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-1006-1 · Cited by 145
Metformin treatment rescues CD8+ T-cell response to immune checkpoint inhibitor therapy in mice with NAFLD
Wabitsch, S., McCallen, J., Kamenyeva, O., Ruf, B., McVey, J. C., Kabát, J., Walz, J. S., Rotman, Y., Bauer, K. C., Craig, A. J., et al. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.03.010 · Cited by 147
Myalgic encephalomyelitis/chronic fatigue syndrome patients exhibit altered T cell metabolism and cytokine associations
Mandarano, A. H., Maya, J., Giloteaux, L., Peterson, D. L., Maynard, M., Gottschalk, C. G., & Hanson, M. R. (2019) · Journal of Clinical Investigation · doi:10.1172/jci132185 · Cited by 149
Methylation across the central dogma in health and diseases: new therapeutic strategies
Liu, R., Zhao, E., Yu, H., Yuan, C., Abbas, M. N., & Cui, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01528-y · Cited by 155
Non-conventional Inhibitory CD4+Foxp3−PD-1hi T Cells as a Biomarker of Immune Checkpoint Blockade Activity
Zappasodi, R., Budhu, S., Hellmann, M. D., Postow, M. A., Senbabaoglu, Y., Manne, S., Gasmi, B., Liu, C., Zhong, H., Li, Y., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.05.009 · Cited by 142
Self-citation
Immunotherapy against cancer-related viruses
Tashiro, H., & Brenner, M. K. (2016) · Cell Research · doi:10.1038/cr.2016.153 · Cited by 147
Eomes-Dependent Loss of the Co-activating Receptor CD226 Restrains CD8+ T Cell Anti-tumor Functions and Limits the Efficacy of Cancer Immunotherapy
Weulersse, M., Asrir, A., Pichler, A., Lemaitre, L., Braun, M., Carrié, N., Joubert, M.-V., Moine, M. L., Souto, L. D., Gaud, G., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.09.006 · Cited by 148
Non-terminally exhausted tumor-resident memory HBV-specific T cell responses correlate with relapse-free survival in hepatocellular carcinoma
Cheng, Y., Gunasegaran, B., Singh, H. D., Dutertre, C.-A., Loh, C. Y., Lim, J. Q., Crawford, J. C., Lee, H. K., Zhang, X., Lee, B., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.06.013 · Cited by 142
Clonal Deletion of Tumor-Specific T Cells by Interferon-γ Confers Therapeutic Resistance to Combination Immune Checkpoint Blockade
Pai, C.-C. S., Huang, J. T., Lu, X., Simons, D. M., Park, C., Chang, A., Tamaki, W., Liu, E., Roybal, K. T., Seagal, J., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.01.006 · Cited by 141
Combined GS-4774 and Tenofovir Therapy Can Improve HBV-Specific T-Cell Responses in Patients With Chronic Hepatitis
Boni, C., Janssen, H. L. A., Rossi, M., Yoon, S. K., Vecchi, A. L., Barili, V., Yoshida, E. M., Trinh, H. N., Rodell, T. C., Laccabue, D., et al. (2019) · Gastroenterology · doi:10.1053/j.gastro.2019.03.044 · Cited by 141
Blockade of interleukin 10 potentiates antitumour immune function in human colorectal cancer liver metastases
Sullivan, K. M., Jiang, X., Guha, P., Lausted, C. G., Carter, J. A., Hsu, C. L., Labadie, K. P., Kohli, K., Kenerson, H. L., Daniel, S. K., et al. (2022) · Gut · doi:10.1136/gutjnl-2021-325808 · Cited by 142
Exhaustion of T lymphocytes in the tumor microenvironment: Significance and effective mechanisms
Gholami, M. D., Kardar, G. A., Saeedi, Y., Heidari, S., Garssen, J., & Falak, R. (2017) · Cellular Immunology · doi:10.1016/j.cellimm.2017.10.002 · Cited by 143
Single-Cell Lymphocyte Heterogeneity in Advanced Cutaneous T-cell Lymphoma Skin Tumors
Gaydosik, A. M., Tabib, T., Geskin, L. J., Bayan, C.-A. Y., Conway, J. F., Lafyatis, R., & Fuschiotti, P. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-0148 · Cited by 140
Characterization of Immune Dysfunction and Identification of Prognostic Immune-Related Risk Factors in Acute Myeloid Leukemia
Tang, L., Wu, J., Li, C.-G., Jiang, H., Xu, M., Du, M., Yin, Z., Mei, H., & Hu, Y. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-3003 · Cited by 140
Heterogeneity of immune cells in human atherosclerosis revealed by scRNA-Seq
Vallejo, J., Cochain, C., Zernecke, A., & Ley, K. F. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab260 · Cited by 143
Co-Stimulatory Receptor Signaling in CAR-T Cells
Honikel, M. M., & Olejniczak, S. H. (2022) · Biomolecules · doi:10.3390/biom12091303 · Cited by 149
First-dose mRNA vaccination is sufficient to reactivate immunological memory to SARS-CoV-2 in subjects who have recovered from COVID-19
Mazzoni, A., Di Lauria, N., Maggi, L., Salvati, L., Vanni, A., Capone, M., Lamacchia, G., Mantengoli, E., Spinicci, M., Zammarchi, L., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci149150 · Cited by 139
Tumour microenvironment responsive nanoconstructs for cancer theranostic
Gulzar, A., Xu, J., Wang, C., He, F., Yang, D., Gai, S., Yang, P., Lin, J., Jin, D., & Xing, B. (2019) · Nano Today · doi:10.1016/j.nantod.2019.03.007 · Cited by 141
A Burned-Out CD8+ T-cell Subset Expands in the Tumor Microenvironment and Curbs Cancer Immunotherapy
Sanmamed, M. F., Nie, X., Desai, S., Villarroel‐Espíndola, F., Badri, T., Zhao, D., Kim, A. W., Ji, L., Zhang, T., Quinlan, E., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0962 · Cited by 140
Localization, tissue biology and T cell state — implications for cancer immunotherapy
Schenkel, J. M., & Pauken, K. E. (2023) · Nature reviews. Immunology · doi:10.1038/s41577-023-00884-8 · Cited by 144
Gamma delta T-cell-based immune checkpoint therapy: attractive candidate for antitumor treatment
Gao, Z., Bai, Y., Lin, A., Jiang, A., Zhou, C., Cheng, Q., Liu, Z., Chen, X., Zhang, J., & Luo, P. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01722-0 · Cited by 138

Authors: Wherry, E. J., & Kurachi, M.
Affiliations: University of Pennsylvania (US)
Corresponding author: Wherry, E. John
Kurachi, Makoto
ORCID: Wherry, E. John
Kurachi, Makoto
Venue: Nature Reviews Immunology
Publisher: Springer Science and Business Media LLC
Published: 2015-07-24
Volume: 15
Issue: 8
Pages: 486-499
ISSN: 1474-1733 (ISSN-L)
1474-1741
DOI: 10.1038/nri3862
PMC: PMC4889009
OpenAlex: W1910012553
Cited by: 4,652
References: 156
Citations by year: 2026: 563 · 2025: 494 · 2024: 518 · 2023: 508 · 2022: 517 · 2021: 551 · 2020: 441 · 2019: 381 · 2018: 306 · 2017: 227 · 2016: 129 · 2015: 12
FWCI: 21.14
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature reviews. Immunology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: U.S. Public Health Service (HHSN266200500030C)
National Institute of Allergy and Infectious Diseases (HHSN266200500030C, AI 082630, R01AI105343, AI095608, AI105343, AI112521, P01AI112521, U01AI095608, U19AI082630)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
Keywords: T cell exhaustion, chronic viral infection, cancer immunotherapy, inhibitory receptors, persistent antigen, inflammatory signals, transcriptional programs, therapeutic target
MeSH terms: Bacterial Infections, Gene Expression Regulation, Humans, Immunologic Memory, Lymphocyte Activation, Neoplasms, T-Lymphocytes, Cytotoxic, Transcription, Genetic, Virus Diseases, Signal Transduction, Cytokines, Clonal Anergy, CD57 Antigens, T-Lymphocytes, Regulatory

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Molecular and cellular insights into T cell exhaustion

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks