Cited by 866T-cell and B-cell ImmunologySignaling Pathways in DiseaseCancer Immunotherapy and Biomarkers

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The Transcription Factor NFAT Promotes Exhaustion of Activated CD8 + T Cells

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Martinez, Gustavo J., Pereira, Renata M., Äijö, Tarmo, Kim, Edward Y., Marangoni, Francesco, Pipkin, Matthew E., Togher, Susan, Heissmeyer, Vigo, Zhang, Yi Chen, Crotty, Shane, Lamperti, Edward D., Ansel, K. Mark, Mempel, Thorsten R., Lähdesmäki, Harri, Hogan, Patrick G., Rao, Anjana·2015·Immunity

DOI 10.1016/j.immuni.2015.01.006PMC PMC4346317

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Abstract

During persistent antigen stimulation, CD8(+) T cells show a gradual decrease in effector function, referred to as exhaustion, which impairs responses in the setting of tumors and infections. Here we demonstrate that the transcription factor NFAT controls the program of T cell exhaustion. When expressed in cells, an engineered form of NFAT1 unable to interact with AP-1 transcription factors diminished T cell receptor (TCR) signaling, increased the expression of inhibitory cell surface receptors, and interfered with the ability of CD8(+) T cells to protect against Listeria infection and attenuate tumor growth in vivo. We defined the genomic regions occupied by endogenous and engineered NFAT1 in primary CD8(+) T cells and showed that genes directly induced by the engineered NFAT1 overlapped with genes expressed in exhausted CD8(+) T cells in vivo. Our data show that NFAT promotes T cell anergy and exhaustion by binding at sites that do not require cooperation with AP-1.

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Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849 · cited 1×
“Barcoded librarieswere sequenced in aSOLID4 sequencer (Applied Biosystems) and the reads were mapped by Bowtie (Langmead et al., 2009) to the mm9 genome in color-space.”
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Damm, T. B., & Egli, M. (2014) · Cellular Physiology and Biochemistry · doi:10.1159/000356667 · Cited by 14,552
TopHat: discovering splice junctions with RNA-Seq
Trapnell, C., Pachter, L. S., & Salzberg, S. L. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp120 · Cited by 11,682
T cell exhaustion
Wherry, E. J. (2011) · Nature Immunology · doi:10.1038/ni.2035 · Cited by 4,062 · cited 15×
“, 2011), and in CD8 T cells in the context of prolonged low-grade antigenic stimulation and/or inflammation, as encountered in chronic viral infections and cancer (Schietinger and Greenberg, 2014; Wherry, 2011).”
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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 · cited 4×
“, 2006), and blocking this pathway during chronic LCMV infection reinvigorates virus-specific CD8 T cell responses, resulting in lower viral loads (Barber et al., 2006).”
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TRANSCRIPTION FACTORS OF THE NFAT FAMILY:Regulation and Function
Rao, A., Luo, C. H., & Hogan, P. G. (1997) · Annual Review of Immunology · doi:10.1146/annurev.immunol.15.1.707 · Cited by 2,592 · cited 2×
“Notably, most NFAT1 ChIP-seq peaks did not overlap with CARIT-NFAT1 ChIP-seq peaks (Figure 4A, left and middle), suggesting that at these sites, NFAT binding is strongly stabilized by AP-1 (probably by 20-fold ormore) (Rao et al., 1997).”
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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 · cited 14×
“…in CD8+ and CD4+ T cells by CA-RIT-NFAT1 and those observed in exhausted CD8+ T cells and anergic CD4+ T cells in vivo (22/56 genes and 99/371 genes, respectively; p value < 10 10) (Figures 2E, 2F, and S3E; Tables 1, S1, and S2; Doering et al., 2012; Okamura et al., 2009; Wherry et al., 2007).”
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“Moreover, antibodies to PD-1 and CTLA-4 have emerged as surprisingly effective agents for cancer immunotherapy (Schietinger and Greenberg, 2014), and individual or combined blockade of TIM3, PD-1, and LAG3 with antagonist antibodies has been shown to reverse exhaustion efficiently in CD8 T cells (Blackburn et al., 200…”
Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection
Blackburn, S. D., Shin, H., Haining, W. N., Zou, T., Workman, C. J., Polley, A., Betts, M. R., Freeman, G. J., Vignali, D. A. A., & Wherry, E. J. (2009) · Nature Immunology · doi:10.1038/ni.1679 · Cited by 2,062 · cited 2×
“Moreover, antibodies to PD-1 and CTLA-4 have emerged as surprisingly effective agents for cancer immunotherapy (Schietinger and Greenberg, 2014), and individual or combined blockade of TIM3, PD-1, and LAG3 with antagonist antibodies has been shown to reverse exhaustion efficiently in CD8 T cells (Blackburn et al., 200…”
Transcriptional regulation by calcium, calcineurin, and NFAT
Hogan, P. G., Chen, L., Nardone, J., & Rao, A. (2003) · Genes & Development · doi:10.1101/gad.1102703 · Cited by 1,991 · cited 3×
“The ability to participate inmultiple transcriptional complexes allows NFAT to contribute to different transcriptional programs depending on the cell type and signaling context in which it is activated (Hogan et al., 2003).”
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“[62] Martinez GJ, Pereira RM, Aijo T, Kim EY, Marangoni F, Pipkin ME, et al.”
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“…of transcription factors in favour of NFAT is also implicated in the induction of these states (Maci (cid:1) an et al , 2002; Wells, 2009; Martinez et al , 2015), so it is not surprising that TNFRSF co-stimulation has been reported to counter-act both anergy and exhaustion in vivo…”
Hierarchical transcriptional network governing heterogeneous T cell exhaustion and its implications for immune checkpoint blockade
Tian, W., Qin, G., Jia, M., Li, W., Cai, W., Wang, H., Zhao, Y., Bao, X., Wei, W., Zhang, Y., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1198551 · Cited by 16
Self-citation
The Dual Role of the NFATc2/galectin‐9 Axis in Modulating Tumor‐Initiating Cell Phenotypes and Immune Suppression in Lung Adenocarcinoma
Xiao, Z., Wang, S., Chen, J., Li, Y., Jiang, Y., Tin, V. P., Liu, J. S., Hu, H., Wong, M. P., Pan, Y., et al. (2024) · Advanced Science · doi:10.1002/advs.202306059 · Cited by 14
The new era of immunological treatment, last updated and future consideration of CAR T cell-based drugs
Hadiloo, K., Taremi, S., Safa, S. H., Amidifar, S., & Esmaeilzadeh, A. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107158 · Cited by 14
BET inhibition reforms the immune microenvironment and alleviates T cell dysfunction in chronic lymphocytic leukemia
Smith, A. L., Skupa, S. A., Eiken, A. P., Reznicek, T. E., Schmitz, E. G., Williams, N., Moore, D. Y., D'Angelo, C. R., Kallam, A., Lunning, M. A., et al. (2024) · JCI Insight · doi:10.1172/jci.insight.177054 · Cited by 14
“…treatment also included those associated with immune activation (Stat, IRF, and RHD families) (62–65) as well as those present in more differentiated cells (retinoic acid receptors DR5 motif) (66) and binding motifs for TFs that can cooperate to drive T cell exhaustion (NFAT, BATF, IRF4) (65, 67).”
Background
Synthesis and characterization of soquelitinib a selective ITK inhibitor that modulates tumor immunity
Hsu, L., Rosenbaum, J. T., Verner, E. J., Jones, W. B., Hill, C. M., Janc, J. W., Buggy, J. J., Pawar, R. D., Ghosh, P., Li, D., et al. (2024) · npj Drug Discovery. · doi:10.1038/s44386-024-00002-1 · Cited by 12
A key control point in the T cell response to chronic infection and neoplasia: FOXO1
Marcel, N., & Hedrick, S. Μ. (2020) · Current Opinion in Immunology · doi:10.1016/j.coi.2020.02.001 · Cited by 16
Activin-A impedes the establishment of CD4+ T cell exhaustion and enhances anti-tumor immunity in the lung
Morianos, I., Tsitsopoulou, A., Potaris, Κ., Valakos, D., Fari, O., Vatsellas, G., Bostantzoglou, C., Photiades, A., Gaga, M., Xanthou, G., et al. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-02092-5 · Cited by 15
LARP4-mediated hypertranslation drives T cell dysfunction in tumors
Liu, Y., Ni, H., Li, J., Yang, J., Sekielyk, I., Snow, B. E., Zhang, Z., Zhang, F., Paul, M. S., Han, J., et al. (2025) · Nature Immunology · doi:10.1038/s41590-025-02232-5 · Cited by 18
Self-citation
Gzmk+ CD8 T cells in inflammatory diseases
Cui, X., Liu, P., Zhan, Q., & Cao, W. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1661755 · Cited by 16
Transcriptional regulator SATB1 limits CD8+ T cell population expansion and effector differentiation in chronic infection and cancer
Heyden, L., Rausch, L., Shannon, M. H., Dryburgh, L., Moreira, M. L., Frolov, A., Scheffler, C. M., van Elsas, M. J., Tong, J., Hidajat, O., et al. (2025) · Nature Immunology · doi:10.1038/s41590-025-02316-2 · Cited by 14
“T cell exhaustion is driven by persistent antigen exposure, which leads to the high and persistent expression of T cell antigen receptor (TCR)-signaling-induced transcription factors, such as NFATC1, IRF4, BATF, NR4A and TOX 3–5 , 10–16 .”
Chronic LCMV Infection Is Fortified with Versatile Tactics to Suppress Host T Cell Immunity and Establish Viral Persistence
Studstill, C. J., & Hahm, B. (2021) · Viruses · doi:10.3390/v13101951 · Cited by 15
“As a result, NFAT-deficient mice were shown to have fewer virus-specific CD8+ T cells expressing PD-1, Tim-3, and LAG-3 during LCMV infection [113,114].”
Background
Put in a “Ca2+ll” to Acute Myeloid Leukemia
Lewuillon, C., Laguillaumie, M.-O., Quesnel, B., Idziorek, T., Touil, Y. S., & Lemonnier, L. (2022) · Cells · doi:10.3390/cells11030543 · Cited by 16
Biallelic NFATC1 mutations cause an inborn error of immunity with impaired CD8+ T-cell function and perturbed glycolysis
Bal, S. K., Giuliani, S., Block, J., Repiščák, P., Hafemeister, C., Shahin, T., Kasap, N., Ransmayr, B., Miao, Y., van de Wetering, C., et al. (2023) · Blood · doi:10.1182/blood.2022018303 · Cited by 17
Tumor-Reactive CD8+ T Cells Enter a TCF1+PD-1− Dysfunctional State
Roetman, J. J., Erwin, M. M., Rudloff, M. W., Favret, N. R., Román, C. R. D., Apostolova, M. K. I., Murray, K. A., Lee, T., Lee, Y. A., & Philip, M. (2023) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-22-0939 · Cited by 13
Nr4a1 and Nr4a3 redundantly control clonal deletion and contribute to an anergy-like transcriptome in auto-reactive thymocytes to impose tolerance in mice
Nielsen, H. V., Yang, L., Mueller, J. L., Ritter, A. J., Hiwa, R., Proekt, I., Rackaityte, E., Aylard, D. A., Gupta, M., Scharer, C. D., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-55839-5 · Cited by 12
“Anjana Rao and colleagues showed that a constitutively active form of NFAT that cannot cooperate with AP-1 (CA-NFAT-RIT) drives an anergic transcriptional program 72 .”
Targeting Transcriptional Regulators of CD8+ T Cell Dysfunction to Boost Anti-Tumor Immunity
Waugh, K. A., Leach, S. M., & Slansky, J. E. (2015) · Vaccines · doi:10.3390/vaccines3030771 · Cited by 14
“NFAT1 mutant incapable of binding AP-1 decreases TCR signaling and promotes exhaustion to result in uncontrolled infection and tumor growth [151].”
Background
TGF-β-p-STAT1-LAIR2 axis has a “self-rescue” role for exhausted CD8+ T cells in hepatocellular carcinoma
Pan, B., Wang, Z., Yao, Y., Ke, X., Shen, S., Chen, W., Zhang, X., Qiu, J., Wu, X., & Tang, N. (2023) · Cellular Oncology · doi:10.1007/s13402-023-00830-9 · Cited by 13
Enhanced STAT5a activation rewires exhausted CD8 T cells during chronic stimulation to acquire a hybrid durable effector like statePreprint
Beltra, J., Abdel-Hakeem, M. S., Manne, S., Zhang, Z., Huang, H., Kurachi, M., Su, L., Picton, L. K., Muroyama, Y., Casella, V., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.10.03.509766 · Cited by 13
CD8+ T cell stressors converge on shared metabolic–epigenetic networks
Shangguan, Y., Wang, J., Ho, P., & Xu, Y. (2025) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2025.08.009 · Cited by 14
Enhanced FOS expression improves tumor clearance and resists exhaustion in NR4A3-deficient CAR T cells under chronic antigen exposure
Yin, P., Yang, J.-G., Jiang, Y., Han, L., Xiong, T.-C., Liu, H., Fang, Y., Ruan, W., Wu, J., Chen, L., et al. (2025) · Science Advances · doi:10.1126/sciadv.adw3571 · Cited by 13
“…showed that NR4A3 KD CAR T cells during CAE displayed up-regulation of several AP-1 (bZIP) family members, including JUNB, JUND, BATF, and BATF3, which have been reported to drive an effector phenotype in T cells, enabling them to secrete large amounts of effector cytokines in tumors ( 30 , 32 ).”
CAR-T cells in solid tumors: engineering, biomarkers, translational pathways and the road ahead
Shaer, N. S. H. A., Masoud, I., Tleyjeh, A., Al-Attas, A. A., Al-Attas, M. A., Khan, M. I., & Yaqinuddin, A. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1796675 · Cited by 15
“A central driver of this state is the NFAT family; under conditions of chronic stimulation, NFAT shifts from forming cooperative heterodimers with AP-1 to forming homodimers, which directly promote the expression of inhibitory receptors such as PD-1, LAG-3, and TIM-3 (93 – 95).”
Galectin-3 expression in donor T cells reduces GvHD severity and lethality after allogeneic hematopoietic cell transplantation
Mohammadpour, H., Tsuji, T., MacDonald, C. R., Sarow, J. L., Rosenheck, H. R., Daneshmandi, S., Choi, J. E., Qiu, J., Matsuzaki, J., Witkiewicz, A. K., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112250 · Cited by 12
The activation of CaN/NFAT signaling pathway in macrophages aggravated Lactobacillus casei cell wall extract-induced Kawasaki disease vasculitis
Sun, Y., Tao, Y., Geng, Z., Zheng, F., Wang, Y., Wang, Y., Fu, S., Wang, W., Xie, C., Zhang, Y., et al. (2023) · Cytokine · doi:10.1016/j.cyto.2023.156304 · Cited by 12
Self-citation
Co-stimulation of CD28/CD40 signaling molecule potentiates CAR-T cell efficacy and stemness
Khopanlert, W., Choochuen, P., Maneechai, K., Jangphattananont, N., Ung, S., Okuno, S., Steinberger, P., Leitner, J. M., Sangkhathat, S., Viboonjuntra, P., et al. (2024) · Molecular Therapy Oncology · doi:10.1016/j.omton.2024.200837 · Cited by 12
Genetical engineering for NK and T cell immunotherapy with CRISPR/Cas9 technology: Implications and challenges
Zhi, L., Su, X., Yin, M., Zhang, Z., Lü, H., Niu, Z., Guo, C., Zhu, W., & Zhang, X. (2021) · Cellular Immunology · doi:10.1016/j.cellimm.2021.104436 · Cited by 13
Silencing and activating anergic B cells*
Tanaka, S., Ise, W., Baba, Y., & Kurosaki, T. (2021) · Immunological Reviews · doi:10.1111/imr.13053 · Cited by 12
The expression pattern of Immune checkpoints after chemo/radiotherapy in the tumor microenvironment
Hassanian, H., Asadzadeh, Z., Baghbanzadeh, A., Derakhshani, A., Dufour, A., Khosroshahi, N. R., Najafi, S., Brunetti, O., Silvestris, N., & Baradaran, B. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.938063 · Cited by 12
“Exhausted CD8+ T cells do not proliferate well because they have impaired killing activity and secrete Low levels of effector cytokines such as INF-g and TNF-a (45).”
Background
T‐cell heterogeneity, progenitor–progeny relationships, and function during latent and chronic viral infections
Sandu, I., & Oxenius, A. (2023) · Immunological Reviews · doi:10.1111/imr.13203 · Cited by 14
Regulation of CD19 CAR-T cell activation based on an engineered downstream transcription factor
Lainšček, D., Golob-Urbanc, A., Mikolič, V., Pantović-Žalig, J., Malenšek, Š., & Jerala, R. (2023) · Molecular Therapy — Oncolytics · doi:10.1016/j.omto.2023.04.005 · Cited by 12
“NFAT plays a complex role in T cells; as the constitutively active NFAT can drive T cell anergy and exhaustion by upregulating genes for the inhibitory surface molecule expression, such as PD-1, LAG3, CTLA-4, and so on.(64,65) Despite that, we did not observe impaired IL2 secretion, which is also one of the hallmarks…”
Background
Loss of NFAT2 expression results in the acceleration of clonal evolution in chronic lymphocytic leukemia
Müller, D. J., Wirths, S., Fuchs, A. R., Märklin, M., Heitmann, J. S., Sturm, M., Haap, M. M., Kirschniak, A., Sasaki, Y., Kanz, L., et al. (2018) · Journal of Leukocyte Biology · doi:10.1002/jlb.2ab0218-076rr · Cited by 12
Role of Nurr1 in Carcinogenesis and Tumor Immunology: A State of the Art Review
Wan, P. K.-T., Siu, M. K.-Y., Leung, T. H.-Y., Mo, X.-T., Chan, K. K. L., & Ngan, H. (2020) · Cancers · doi:10.3390/cancers12103044 · Cited by 12
“In addition, enrichment of the consensus binding motif for transcription factors associated with T cell activation i.e., NFAT: AP-1 composite site, and consensus binding motif for NFAT without an AP-1 site are observed.”
BackgroundInfluential
Transcription factor NFAT1 controls allergic contact hypersensitivity through regulation of activation induced cell death program
Kwon, H., Kim, G.-C., Hwang, J. S., Kim, Y., Chae, C.-S., Nam, J. H., Jun, C., Rudra, D., Surh, C. D., & Im, S. (2016) · Scientific Reports · doi:10.1038/srep19453 · Cited by 12
STIM1-mediated NFAT signaling synergizes with STAT1 to control T-bet expression and TH1 differentiation
Zhong, L., Wang, Y., Kahlfuß, S., Jishage, M., McDermott, M., Yang, J. J. J., Tao, A. Y., Hu, K., Noyer, L., Raphael, D., et al. (2025) · Nature Immunology · doi:10.1038/s41590-025-02089-8 · Cited by 13
“We analyzed the binding of NFATc2 to the Tbx21 locus using ChIP–seq data from Nfatc2 −/− CD8 + T cells 34 and that of NFATc1 using ChIP–seq data from CD8 + T cells of a BAC-transgenic mouse strain in which NFATc1 is endogenously biotinylated by the biotin-ligase BirA 35 .”
T cell aging and exhaustion: Mechanisms and clinical implications
Zhang, W., Kong, D., Zhang, X., Hu, L., Nian, Y., & Shen, Z. (2025) · Clinical Immunology · doi:10.1016/j.clim.2025.110486 · Cited by 13
CD8+ T cell-based immunotherapy: Promising frontier in human diseases
Ton, N. Q. C., Deka, G., & Park, P. (2025) · Biochemical Pharmacology · doi:10.1016/j.bcp.2025.116909 · Cited by 12
NFAT1 Regulates Systemic Autoimmunity through the Modulation of a Dendritic Cell Property
Chae, C.-S., Kim, G.-C., Park, E. S., Lee, C., Verma, R. P., Cho, H., Jun, C., Yoo, Y. J., & Im, S. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1700882 · Cited by 11
“haustion programs, depending on the nature of its binding partners (12).”
Background
IL-21 in Homeostasis of Resident Memory and Exhausted CD8 T Cells during Persistent Infection
Ren, H. M., & Lukacher, A. E. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186966 · Cited by 13
Chromatin-embedded reporter genes: Quantification of stimulus-induced gene transcription
Thiel, G., Backes, T. M., Guethlein, L. A., & Rößler, O. G. (2021) · Gene · doi:10.1016/j.gene.2021.145645 · Cited by 11
Remodeling the chromatin landscape in T lymphocytes by a division of labor among transcription factors
Vahedi, G. (2021) · Immunological Reviews · doi:10.1111/imr.12942 · Cited by 11
Metabolic Screening of Cytotoxic T-cell Effector Function Reveals the Role of CRAC Channels in Regulating Lethal Hit Delivery
Slaats, J., Dieteren, C. E. J., Wagena, E., Wolf, L., Raaijmakers, T. K., van der Laak, J. A. W. M., Figdor, C. G., Weigelin, B., & Friedl, P. (2021) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-20-0741 · Cited by 11
“NFAT is a critical transcriptional regulator of the CTL effector response, mediating T-cell proliferation and inhibitory checkpoint expression upon persistent antigenic stimulation (34, 35).”
Background
T‐cell exhaustion from a multiomics perspective: Differentiation mechanisms and regulatory networks in the journey from progenitor‐Exhausted T cells to terminally exhausted T cells
Zhu, T., Teng, X., Jiao, Q., Ren, Y., Wang, Y., & Feng, M. (2026) · Clinical and Translational Medicine · doi:10.1002/ctm2.70609 · Cited by 12
“72 In this unopposed state, NFAT directly transactivates genes central to the exhaustion programme, including the IR PD-1 (via its Pdcd1 promoter) and the transcription factors NR4A and TOX.”
Immune Checkpoints in Solid Organ Transplantation
Bello, A. D., & Treiner, E. (2023) · Biology · doi:10.3390/biology12101358 · Cited by 10
“Similarly, NFAT promotes T cell exhaustion in CD8 T cells, suggesting that calcineurin inhibitors, which block NFAT translocation, can be harmful to exhaustion induction [123].”
Background
HELIOS-expressing human CD8 T cells exhibit limited effector functions
Neyens, D., Hirsch, T., Hadi, A. A. A. I. A., Dauguet, N., Vanhaver, C., Bayard, A., Wildmann, C., Luyckx, M., Squifflet, J.-L., D’Hondt, Q., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1308539 · Cited by 10
Multiomics integration-based immunological characterizations of adamantinomatous craniopharyngioma in relation to keratinization
Xu, C., Wu, J., Ye, J., Si, Y., Zhang, J., Wu, B., Pan, L., Fu, J., Quan, R., Xie, S., et al. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06840-1 · Cited by 13
“2J and S1F) [22].”

Authors: Martinez, G. J., Pereira, R. M., Äijö, T., Kim, E. Y., Marangoni, F., Pipkin, M. E., Togher, S., Heissmeyer, V., Zhang, Y. C., Crotty, S., Lamperti, E. D., Ansel, K. M., Mempel, T. R., Lähdesmäki, H., Hogan, P. G., & Rao, A.
Affiliations: La Jolla Institute for Immunology (US)
Harvard University (US)
Scripps Research Institute (US)
Helmholtz Munich (DE)
St. Luke's-Roosevelt Hospital Center (US)
Boston Children's Hospital (US)
University of California, San Francisco (US)
Aalto University (FI)
Corresponding author: Lähdesmäki, Harri
Rao, Anjana
ORCID: Pereira, Renata M.
Äijö, Tarmo
Kim, Edward Y.
Marangoni, Francesco
Pipkin, Matthew E.
Heissmeyer, Vigo
Crotty, Shane
Lamperti, Edward D.
Ansel, K. Mark
Mempel, Thorsten R.
Lähdesmäki, Harri
Hogan, Patrick G.
Rao, Anjana
Venue: Immunity
Publisher: Elsevier BV
Published: 2015-02
Volume: 42
Issue: 2
Pages: 265-278
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2015.01.006
PMC: PMC4346317
OpenAlex: W2018775174
Cited by: 857
References: 52
Citations by year: 2026: 104 · 2025: 97 · 2024: 110 · 2023: 104 · 2022: 84 · 2021: 95 · 2020: 84 · 2019: 69 · 2018: 30 · 2017: 37 · 2016: 26 · 2015: 17
FWCI: 18.04
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 381 d)
Locations: Immunity (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Site cant be reached (submittedVersion)
PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
Funders: National Cancer Institute (R01CA150975, U19CA179563, R01CA042471, R01 CA-42471)
National Institute of Allergy and Infectious Diseases (R01 AI40127, R01AI072543, R01AI095634, AI84167, U19AI109976, R01AI084167, R01AI109842, R01AI040127)
National Institute of Diabetes and Digestive and Kidney Diseases (P30DK043351)
National Center for Research Resources (S10RR027366)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords: NFAT1, T cell exhaustion, CD8+ T cells, T cell anergy, T cell receptor signaling, AP-1, inhibitory receptors, listeriosis, antitumor immunity, transcriptional regulation
MeSH terms: Animals, Cells, Cultured, Gene Expression Regulation, Listeriosis, Listeria monocytogenes, Lymphocyte Activation, Mice, Transgenic, Neoplasms, Promoter Regions, Genetic, Receptors, Antigen, T-Cell, Recombinant Proteins, Clonal Anergy, CD8-Positive T-Lymphocytes, Transcription Factor AP-1, NFATC Transcription Factors, Mice

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The Transcription Factor NFAT Promotes Exhaustion of Activated CD8 + T Cells

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