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The Transcription Factor NFAT Promotes Exhaustion of Activated CD8 + T Cells
Open accessAbstract
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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“Exhausted cells presented a high activity of Nfatc1 regulon, which is presumably involved in regulating the exhaustion process (50–53).”
From Aging promotes reorganization of the CD4 T cell landscape toward extreme regulatory and effector phenotypes (2019) · cites this paper as [51]
In the citing paper
“TCR-induced Ca2+–NFAT signaling is indispensable for T cell exhaustion and induces the expression of inhibitory surface receptors, such as PD-1, Lag-3 and Tim-3 (ref. 43).”
From Tumor-specific cholinergic CD4+ T lymphocytes guide immunosurveillance of hepatocellular carcinoma (2023) · cites this paper as [43]
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InfluentialRestoring function in exhausted CD8 T cells during chronic viral infection
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InfluentialTRANSCRIPTION FACTORS OF THE NFAT FAMILY:Regulation and Function
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“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).”
Self-citationMolecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
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“…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).”
InfluentialTargeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity
Sakuishi, K., Apetoh, L., Sullivan, J. M., Blazar, B. R., Kuchroo, V. K., & Anderson, A. C. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20100643 · Cited by 2,072 · 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…”
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
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“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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“In addition to the absence of nuclear NFAT in exhausted CD8+ T-cells, alteration in the balance of NFAT and its binding partner AP-1 has dramatic effects on the targeted transcriptional program (48).”
BackgroundUrolithin A Hijacks ERK1/2‐ULK1 Cascade to Improve CD8+ T Cell Fitness for Antitumor Immunity
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“antigen-dependent activation of TCR signaling, leading to two events: (1) the sustained overexpression of TCR-responsive IRF4 and its binding partners, mainly AP1 family members, including BATF, BATF3, JunB and JunD (24, 35, 89–92), as well as nuclear factor of activated T cells (NFAT), a key regulator of T cell activ…”
BackgroundMesenchymal cells in the Lung: Evolving concepts and their role in fibrosis
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“TOX is induced through the Calcineurin-NFAT2 pathway (Macian, 2005; Martinez et al., 2015; Klein-Hessling et al., 2017), but its maintenance is Calcineurin independent in the late-stage (Khan et al., 2019).”
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Osteoimmunology: Influence of the Immune System on Bone Regeneration and Consumption
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“Moreover, a role for fetal microchimerism or persistent antigen presentation after pregnancy (McCloskey et al., 2011) cannot be excluded.”
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DGKA Mediates Resistance to PD-1 Blockade
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T Cells Control Chemokine Secretion by Keratinocytes
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“In line with the previous report (Martinez et al., 2015), WT, CA-RIT-Nfat1, and DBDmut-Nfat1 were not massively overexpressed relative to endogenous NFAT1 in 15P-1Lmcd1−/− cells (Figure 8a).”
BackgroundSelf-citationDevelopmental partitioning of SYK and ZAP70 prevents autoimmunity and cancer
Sadras, T., Martin, M., Kume, K., Robinson, M. E., Saravanakumar, S., Lenz, G., Chen, Z., Song, J. Y., Siddiqi, T., Oksa, L., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.03.043 · Cited by 33
Beyond T-cell subsets: stemness and adaptation redefining immunity and immunotherapy
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“However, during persistent antigen stimulation, NFAT signaling also PD-1 [126 – 128].”
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“Other TFs critical for the development of T cell exhaustion, such as NR4A family members [73, 90 – 92], NFAT-AP-1 signaling [93 – 96], and BATF/IRF4 [97 – 100], are also associated with TCR signaling.”
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CD69 Imposes Tumor-Specific CD8+ T-cell Fate in Tumor-Draining Lymph Nodes
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From T cell “exhaustion” to anti-cancer immunity
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“In 2018, Arango et al. reported the ‘writer’ protein for ac 4 C, N ‐ acetyltransferase 10 (NAT10), as well as the biological function of ac 4 C in maintaining mRNA stability and promoting translation efficacy.”
The epigenetic landscape of fate decisions in T cells
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“Many transcription factors that regulate various subpopulations of CD8 + T EX cells, such as progenitor, transitory and terminal T EX cells, have been identified, including the HMG-protein TOX, NFAT and NR4A family proteins 24,109,112–115 .”
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“Indeed, when we aligned our DNase-seq data with ChIP-seq data generated using a constitutively active modified form of NFAT1/NFATC2 (CA-RIT-NFAT), which is known to promote exhaustion (Martinez et al., 2015), we observed that NFAT binding was more strongly enriched in the tDHSs (Figures 2C and 2F).”
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“The AP-1 complex is made up of the Fos, Jun, and activating transcription factor protein families [35, 36].”
BackgroundEngineering inducible biomolecular assemblies for genome imaging and manipulation in living cells
Qin, P., Huang, Z., Sun, K., Liu, Y., Yoon, C. W., Harrison, R. E. S., Schmitt, D. L., Zhu, L., Wu, Y., Tasan, I., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-35504-x · Cited by 31
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“Response: We strongly concur with your perspective, and this is indeed a challenge that we are also facing.”
Deciphering the Role of Innate Immune NF-ĸB Pathway in Pancreatic Cancer
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Stem-like CD8+ T cells in cancer
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Impact of Drp1-Mediated Mitochondrial Dynamics on T Cell Immune Modulation
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“Longterm stimulation also increases the level of calcium in T cells and further stimulates the increase in mitochondrial ROS (59, 60) and nuclear factor of activated T cells (NFAT) (61, 62), which can directly activate exhaustion-related transcription factors (63) (Figure 2).”
BackgroundSuppression of Ca2+ signals by EGR4 controls Th1 differentiation and anti‐cancer immunity in vivo
Basu, J. M., Hooper, R., Gross, S., Schultz, B. M., Go, C. K., Samakai, E., Ladner, J., Nicolas, É., Tian, Y., Zhou, B., et al. (2020) · EMBO Reports · doi:10.15252/embr.201948904 · Cited by 25
“Of particular relevance here, the NFAT/AP1 transcription factors bind and regulate the IFN c promoter in the presence of STAT1, STAT4, and STAT5 [24], and the absence of NFAT 1,2 and 4 totally abrogates IFN c production [52].”
Self-citationMarangoni, F., Zhang, R., Mani, V., Thelen, M., Akbar, N. J. A., Warner, R. D., Äijö, T., Zappulli, V., Martínez, G., Turka, L. A., et al. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1701220 · Cited by 24
“In contrast, all tumor-infiltrating WT Treg expressed high levels of ICOS, CTLA, and the cell cycle entry marker Ki67, suggesting that these features are either correlated with or a prerequisite for accumulation in tumor tissue.”
BackgroundMethodInfluentialSelf-citationReceptor signaling, transcriptional, and metabolic regulation of T cell exhaustion
Balkhi, M. Y. (2020) · OncoImmunology · doi:10.1080/2162402x.2020.1747349 · Cited by 26
Wang, J., Zhang, Y., Liu, L., Cui, Z., Shi, R., Hou, J., Liu, Z., Yang, L., Wang, L., & Li, Y. (2020) · BMC Cancer · doi:10.1186/s12885-020-07474-0 · Cited by 25
Self-citationEmerging Approaches for Solid Tumor Treatment Using CAR-T Cell Therapy
Chung, H., Jung, H., & Noh, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222212126 · Cited by 28
Downregulation of TPX2 impairs the antitumor activity of CD8+ T cells in hepatocellular carcinoma
Wang, X., Wang, J., Shen, H., Luo, Z., & Xiao-jie, L. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04645-8 · Cited by 23
Quezada, L. K., Jin, W., Liu, Y. C., Kim, E. S., He, Z., Indralingam, C. S., Tysl, T., Labarta-Bajo, L., Wehrens, E. J., Jo, Y., et al. (2023) · PLoS Biology · doi:10.1371/journal.pbio.3001983 · Cited by 24
Self-citationLucena, P. I., Faget, D. V., Pachulec, E., Robaina, M. C., Klumb, C. E., Robbs, B. K., & Viola, J. P. B. (2015) · Molecular and Cellular Biology · doi:10.1128/mcb.00501-15 · Cited by 26
T cell exhaustion and senescence for ovarian cancer immunotherapy
Zhao, J., Wang, Z., Tian, Y., Ning, J., & Ye, H. (2024) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2024.07.001 · Cited by 26
Phenotypic and spatial heterogeneity of CD8+ tumour infiltrating lymphocytes
Sun, Y., Yinwang, E., Wang, S., Wang, Z., Wang, F., Xue, Y., Zhang, W., Zhao, S., Mou, H., Chen, S., et al. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02104-w · Cited by 29
“NFAT holds critical roles in both T cell activation/ effector function and tolerance/exhaustion, the former of which typically requires partnering of NFAT with AP-1 proteins [93].”
BackgroundJamison, B. L., Lawrance, M. F., Wang, C. J., DeBerg, H. A., Ziegler, L., Sansom, D. M., Gavin, M. A., Walker, L. S. K., & Campbell, D. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114938 · Cited by 24
Immune Modulation in Lung Cancer: Current Concepts and Future Strategies
Gaissmaier, L., & Christopoulos, P. (2020) · Respiration · doi:10.1159/000510385 · Cited by 24
Gene Regulatory Circuits in Innate and Adaptive Immune Cells
Saini, A., Ghoneim, H. E., Lio, C. J., Collins, P. L., & Oltz, E. M. (2022) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101320-025949 · Cited by 24
Armitage, J. D., Newnes, H. V., McDonnell, A. M., Bosco, A., & Waithman, J. C. (2021) · Cells · doi:10.3390/cells10010056 · Cited by 26
The importance of cooperation: Partnerless NFAT induces T cell exhaustion
Bengsch, B., & Wherry, E. J. (2015) · Immunity · doi:10.1016/j.immuni.2015.01.023 · Cited by 23
“In this issue of Immunity, Martinez et al. (2015) demonstrate markedly diminished expression of inhibitory receptors and effector cytokines in activated T cells genetically deficient in NFAT1 and 2.”
BackgroundInfluentialMolecular insight into T cell exhaustion in hepatocellular carcinoma
Zhu, Y., Tan, H., Wang, J., Zhuang, H., Zhao, H., & Lu, X. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107161 · Cited by 28
The role of transforming growth factor-β (TGF-β) in the formation of exhausted CD8 + T cells
Ma, R., Sun, J., & Wang, Y. (2024) · Clinical and Experimental Medicine · doi:10.1007/s10238-024-01394-0 · Cited by 27
“During the development of T cells exhaustion, sustained stimulation of T-cell receptors (TCR) activated transcription factor nuclear factor of activated T cells (NFAT) [26].”
BackgroundChen, X., Ma, C., Li, Y., Liang, Y., Chen, T., Han, D., Luo, D., Zhang, N., Zhao, W., Wang, L., et al. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06944-8 · Cited by 25
Fam102a translocates Runx2 and Rbpjl to facilitate Osterix expression and bone formation
Yamashita, Y., Hayashi, M., Liu, A., Sasaki, F., Tsuchiya, Y., Takayanagi, H., Saito, M., & Nakashima, T. (2025) · Nature Communications · doi:10.1038/s41467-024-55451-z · Cited by 24
T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities
Yang, Y. P., Yao, X., Wang, Q., Yang, M., Li, R., Qin, J., Zhuang, J., & Sun, C. (2026) · Advanced Science · doi:10.1002/advs.202520634 · Cited by 27
Kiuchi, M., Onodera, A., Kokubo, K., Ichikawa, T., Morimoto, Y., Kawakami, E., Takayama, N., Eto, K., Koseki, H., Hirahara, K., et al. (2021) · The Journal of Experimental Medicine · doi:10.1084/jem.20201690 · Cited by 22
AP-1–independent NFAT signaling maintains follicular T cell function in infection and autoimmunity
Seth, A., Yokokura, Y., Choi, J.-Y., Shyer, J. A., Vidyarthi, A., & Craft, J. E. (2023) · The Journal of Experimental Medicine · doi:10.1084/jem.20211110 · Cited by 23
DGKα/ζ inhibition lowers the TCR affinity threshold and potentiates antitumor immunity
Kureshi, R., Bello, E., Kureshi, C. T. S., Walsh, M. J., Lippert, V., Hoffman, M. T., Dougan, M. L., Longmire, T. A., Wichroski, M. J., & Dougan, S. K. (2023) · Science Advances · doi:10.1126/sciadv.adk1853 · Cited by 20
Keshari, S., Shavkunov, A. S., Miao, Q., Saha, A., Minowa, T., Molgora, M., Williams, C. D., Chaib, M., Highsmith, A. M., Pineda, J. E., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114875 · Cited by 28
TCR-induced FOXP3 expression by CD8+ T cells impairs their anti-tumor activity
Lozano, T., Conde, E., Martín-Otal, C., Navarro, F. C., Lasarte-Cía, A., Nasrallah, R., Alignani, D., Gorraiz, M., Sarobe, P., Romero, J. P., et al. (2021) · Cancer Letters · doi:10.1016/j.canlet.2021.12.030 · Cited by 22
Chen, W., Cao, H., Cao, J., Zuo, L., Qu, F., Xu, D., Zhang, H., Gong, H., Chen, J., Ye, J., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04501-9 · Cited by 22
Glycogen synthase kinase 3 controls T-cell exhaustion by regulating NFAT activation
Fu, Y., Wang, J., Liu, C., Liao, K., Gao, X., Tang, R., Binbin, F., Hong, Y., Xiao, N., Xiao, C., et al. (2023) · Cellular and Molecular Immunology · doi:10.1038/s41423-023-01075-0 · Cited by 21
“We found that DKO CD8 + T cells exhibited lower expression levels of T-bet and higher expression levels of PD-1, TIM3, and LAG3 than WT CD8 + T cells (Fig.”
BackgroundMethodInfluentialExhaustion may not be in the human B cell vocabulary, at least not in malaria
Holla, P., Ambegaonkar, A. A., Sohn, H., & Pierce, S. K. (2019) · Immunological Reviews · doi:10.1111/imr.12809 · Cited by 22
Multimodal stimulation screens reveal unique and shared genes limiting T cell fitness
Lin, C., Levy, P. L., Alflen, A., Apriamashvili, G., Ligtenberg, M. A., Vredevoogd, D. W., Bleijerveld, O. B., Alkan, F., Malka, Y., Hoekman, L., et al. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.02.016 · Cited by 21
Mitchell, J. S., Spanier, J. A., Dwyer, A. J., Knutson, T. P., Alkhatib, M. H., Qian, G., Weno, M. E., Chen, Y., Shaheen, Z. R., Tucker, C., et al. (2024) · Immunity · doi:10.1016/j.immuni.2024.07.024 · Cited by 21
Focusing on CD8+ T-cell phenotypes: improving solid tumor therapy
Yao, Z., Zeng, Y., Liu, C., Jin, H., Wang, H., Zhang, Y., Ding, C., Chen, G., & Wu, D. (2024) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-024-03195-5 · Cited by 27
Self-citationTargeting SRSF1 improves cancer immunotherapy by dually acting on CD8+T and tumor cells
Zhu, G., Tang, Z., Chu, T.-H., Wang, B., Chen, S., Tao, C., Cai, J., Yang, R., Qu, W., Wang, Y., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02118-2 · Cited by 23
Pham‐Danis, C., Novak, A. J., Danis, E. P., McClellan, S. M., Leach, L., Yarnell, M. C., Ebmeier, C. C., Tasian, S. K., & Kohler, M. E. (2025) · Cancer Cell · doi:10.1016/j.ccell.2025.02.008 · Cited by 23
Juzans, M., Cuche, C., Rose, T., Mastrogiovanni, M., Bochet, P., Bartolo, V. D., & Alcover, A. (2020) · ImmunoHorizons · doi:10.4049/immunohorizons.2000044 · Cited by 20
Exhausted phenotype of circulating CD8+ T cell subsets in hepatitis B virus carriers
Jiang, D., Chen, C., Yan, D., Zhang, X., Liu, X.-X., Yan, D., Cui, D.-W., & Yang, S.-G. (2022) · BMC Immunology · doi:10.1186/s12865-022-00488-2 · Cited by 19
Modulation of T cell function and survival by the tumor microenvironment
Mani, N. L., Andrews, D., & Obeng, R. C. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1191774 · Cited by 22
“Of note, the T cell exhaustion molecular program, marked by upregulation of TOX and NR4A1, is maintained in stem-like CD8 T cells and is imprinted onto effector progeny derived from the stem-like cells (Utzschneider et al., 2013; Martinez et al., 2015; Pauken et al., 2016; Alfei et al., 2019; Khan et al., 2019; Scott…”
BackgroundPouxvielh, K., Marotel, M., Drouillard, A., Villard, M., Moreews, M., Bossan, A., Poiget, M., Khoryati, L., Benezech, S., Fallone, L., et al. (2024) · Science Advances · doi:10.1126/sciadv.adn0164 · Cited by 25
Oller, J., Alfranca, A., Méndez‐Barbero, N., Villahoz, S., Lozano‐Vidal, N., Martín-Alonso, M., Arroyo, A. G., Escolano, A., Armesilla, A. L., Campanero, M. R., et al. (2015) · Molecular and Cellular Biology · doi:10.1128/mcb.00494-15 · Cited by 21
Towards multiscale modeling of the CD8+T cell response to viral infections
Baral, S., Raja, R., Sen, P., & Dixit, N. M. (2019) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1446 · Cited by 20
“…including NFAT, Maf, Batf, Blimp-1 and Eomes, with the latter inversely correlated with T-bet, have been implicated in CD8 + T cell dysfunction (Buggert et al., 2014; Giordano et al., 2015; Intlekofer et al., 2005; Martinez et al., 2015; Paley et al., 2012; Quigley et al., 2010; Shin et al., 2009).”
BackgroundPriming of transcriptional memory responses via the chromatin accessibility landscape in T cells
Tu, W. J., Hardy, K., Sutton, C. R., McCuaig, R., Li, J., Dunn, J., Tan, A. H. Y., Brezar, V., Morris, M., Denyer, G. S., et al. (2017) · Scientific Reports · doi:10.1038/srep44825 · Cited by 23
The metabolic cross-talk between cancer and T cells
Miguel, S. C.-D., Lucianer, G., & Elia, I. (2023) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2023.03.004 · Cited by 22
Metadata
- 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
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 42
- Issue
- 2
- Pages
- 265-278
- ISSN
- 1074-7613 (ISSN-L)
- 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
- 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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