mTOR Signaling, Tregs and Immune Modulation

Chapman, Nicole M; Chi, Hongbo

doi:10.2217/imt.14.84

Cited by 148T-cell and B-cell ImmunologyPsoriasis: Treatment and PathogenesisCancer Immunotherapy and Biomarkers

mTOR Signaling, Tregs and Immune Modulation

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Chapman, Nicole M, Chi, Hongbo·2014·Immunotherapy

DOI 10.2217/imt.14.84PMC PMC4291176

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Abstract

Foxp3(+) Tregs are central regulators of immune tolerance. As dysregulated Treg responses contribute to disease pathogenesis, novel approaches to target the immunomodulatory functions of Tregs are currently under investigation. mTORC1 and mTORC2 are therapeutic targets of interest. Recent studies revealed that mTOR signaling impacts conventional T-cell homeostasis, activation and differentiation. Moreover, mTOR controls the differentiation and functions of Tregs, suggesting that its activity could be targeted to modulate Treg responses. Here, we summarize how Tregs suppress immune responses, their roles in disease development and methods used to alter their functions therapeutically. We also discuss the diverse effects exerted by mTOR inhibition on the development, homeostasis, and functions of conventional T cells and Tregs. We conclude with a discussion of how modulation of mTOR activity in Tregs may be therapeutically beneficial or detrimental in different disease settings.

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Pharmacological agents that modulate mTOR signaling, including rapamycin, have emerged as promising candidates for restoring immune tolerance and reducing inflammation in chronic liver disease.
“Consequently, pharmacological agents that modulate mTOR signaling, including rapamycin, have emerged as promising candidates for restoring immune tolerance and reducing inflammation in chronic liver disease (Chapman and Chi 2014).”
From The double-edged sword of regulatory T cells in MASLD: from inflammation control to fibrosis promotion (2026) · cites this paper as Chapman and Chi 2014
The Clinical perspectives section (page unavailable) describes mTOR inhibitors, including rapamycin, as potential therapeutics and suggests that targeting mTORC1 in naive T cells may help suppress inflammation. It does not discuss chronic liver disease or establish that these agents restore immune tolerance in that setting. It also cautions that inhibiting mTORC1 in Tregs could worsen inflammation. (LLM, conf=0.88)
Experimental — accuracy not yet measured
mTOR inhibition promotes the induction and maintenance of FOXP3 expression and consequential Treg cell development in humans.
“Interestingly, mTOR inhibition has been described to promote the induction and maintenance of FOXP3 expression and consequential Treg cell development in humans41.”
From Targeting the mTOR pathway uncouples the efficacy and toxicity of PD-1 blockade in renal transplantation (2019) · cites this paper as [41]

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Immunity, Inflammation, and Cancer
Grivennikov, S. I., Greten, F. R., & Karin, M. (2010) · Cell · doi:10.1016/j.cell.2010.01.025 · Cited by 10,755 · see citing works
mTOR Signaling in Growth Control and Disease
Laplante, M., & Sabatini, D. M. (2012) · Cell · doi:10.1016/j.cell.2012.03.017 · Cited by 8,509 · see citing works
Conversion of Peripheral CD4+CD25− Naive T Cells to CD4+CD25+ Regulatory T Cells by TGF-β Induction of Transcription Factor Foxp3
Chen, W., Jin, W., Hardegen, N. J., Lei, K.-J., Li, L., Marinos, N. J., McGrady, G., & Wahl, S. M. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030152 · Cited by 4,678 · see citing works
Innate and adaptive immune cells in the tumor microenvironment
Gajewski, T. F., Schreiber, H., & Fu, Y.-X. (2013) · Nature Immunology · doi:10.1038/ni.2703 · Cited by 4,148 · see citing works
Differentiation of Effector CD4 T Cell Populations
Zhu, J., Yamane, H., & Paul, W. E. (2010) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101212 · Cited by 3,452 · see citing works
CTLA-4 Control over Foxp3 <sup>+</sup> Regulatory T Cell Function
Wing, K., Onishi, Y., Prieto-Martin, P., Yamaguchi, T., Miyara, M., Fehervari, Z., Nomura, T., & Sakaguchi, S. (2008) · Science · doi:10.1126/science.1160062 · Cited by 2,956 · see citing works
Regulatory T cells: mechanisms of differentiation and function
Josefowicz, S. Z., Lu, L.-F., & Rudensky, A. Y. (2012) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141623 · Cited by 2,866 · see citing works
The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1
Sancak, Y., Peterson, T. R., Shaul, Y. D., Lindquist, R. A., Thoreen, C. C., Bar-Peled, L., & Sabatini, D. M. (2008) · Science · doi:10.1126/science.1157535 · Cited by 2,773 · see citing works
Prolonged Rapamycin Treatment Inhibits mTORC2 Assembly and Akt/PKB
Sarbassov, D. D., Ali, S. M., Sengupta, S., Sheen, J.-H., Hsu, P. P., Bagley, A. F., Markhard, A. L., & Sabatini, D. M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.03.029 · Cited by 2,645 · see citing works
Ragulator-Rag Complex Targets mTORC1 to the Lysosomal Surface and Is Necessary for Its Activation by Amino Acids
Sancak, Y., Bar-Peled, L., Zoncu, R., Markhard, A. L., Nada, S., & Sabatini, D. M. (2010) · Cell · doi:10.1016/j.cell.2010.02.024 · Cited by 2,464 · see citing works
FOXP3+ regulatory T cells in the human immune system
Sakaguchi, S., Miyara, M., Costantino, C. M., & Hafler, D. A. (2010) · Nature reviews. Immunology · doi:10.1038/nri2785 · Cited by 2,443 · see citing works
Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression
Lord, G. M., Matarese, G., Howard, J. K., Baker, R. J., Bloom, S. R., & Lechler, R. I. (1998) · Nature · doi:10.1038/29795 · Cited by 2,150 · see citing works
T Cell Activation
Smith-Garvin, J. E., Koretzky, G. A., & Jordan, M. S. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132706 · Cited by 2,144 · see citing works
Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4
Qureshi, O. S., Zheng, Y., Nakamura, K., Attridge, K., Manzotti, C., Schmidt, E. M., Baker, J., Jeffery, L. E., Kaur, S., Briggs, Z., et al. (2011) · Science · doi:10.1126/science.1202947 · Cited by 1,860 · see citing works
A function for interleukin 2 in Foxp3-expressing regulatory T cells
Fontenot, J. D., Rasmussen, J. P., Gavin, M. A., & Rudensky, A. Y. (2005) · Nature Immunology · doi:10.1038/ni1263 · Cited by 1,819 · see citing works
An ATP-competitive Mammalian Target of Rapamycin Inhibitor Reveals Rapamycin-resistant Functions of mTORC1
Thoreen, C. C., Kang, S. A., Chang, J. W., Liu, Q., Zhang, J., Gao, Y., Reichling, L. J., Sim, T., Sabatini, D. M., & Gray, N. S. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m900301200 · Cited by 1,803 · see citing works
mTOR regulates memory CD8 T-cell differentiation
Araki, K., Turner, A. P., Shaffer, V. O., Gangappa, S., Keller, S. A., Bachmann, M. F., Larsen, C. P., & Ahmed, R. (2009) · Nature · doi:10.1038/nature08155 · Cited by 1,575 · see citing works
Enhancing CD8 T-cell memory by modulating fatty acid metabolism
Pearce, E. L., Walsh, M. C., Cejas, P. J., Harms, G. M., Shen, H., Wang, L.-S., Jones, R. G., & Choi, Y. (2009) · Nature · doi:10.1038/nature08097 · Cited by 1,559 · see citing works
Expression of Helios, an Ikaros Transcription Factor Family Member, Differentiates Thymic-Derived from Peripherally Induced Foxp3+ T Regulatory Cells
Thornton, A. M., Korty, P. E., Tran, D. Q., Wohlfert, E. A., Murray, P. E., Belkaid, Y., & Shevach, E. M. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0904028 · Cited by 1,382 · see citing works
Modulation of tryptophan catabolism by regulatory T cells
Fallarino, F., Grohmann, U., Hwang, K. W., Orabona, C., Vacca, C., Bianchi, R., Belladonna, M. L., Fioretti, M. C., Alegre, M., & Puccetti, P. (2003) · Nature Immunology · doi:10.1038/ni1003 · Cited by 1,375 · see citing works
mTOR differentially regulates effector and regulatory T cell lineage commitment
Delgoffe, G. M., Kole, T., Zheng, Y., Zarek, P. E., Matthews, K., Xiao, B., Worley, P., Kozma, S., & Powell, J. (2009) · Immunity · doi:10.1016/j.immuni.2009.04.014 · Cited by 1,293 · see citing works
Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression
Borsellino, G., Kleinewietfeld, M., Mitri, D. D., Sternjak, A., Diamantini, A., Giometto, R., Höpner, S., Centonze, D., Bernardi, G., Dell’Acqua, M. L., et al. (2007) · Blood · doi:10.1182/blood-2006-12-064527 · Cited by 1,287 · see citing works
CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation–mediated apoptosis of effector CD4+ T cells
Pandiyan, P., Zheng, L., Ishihara, S., Reed, J., & Lenardo, M. J. (2007) · Nature Immunology · doi:10.1038/ni1536 · Cited by 1,277 · see citing works
Epigenetic Control of the foxp3 Locus in Regulatory T Cells
Floess, S., Freyer, J., Siewert, C., Baron, U., Olek, S., Polansky, J. K., Schlawe, K., Chang, H., Bopp, T., Schmitt, E., et al. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050038 · Cited by 1,272 · see citing works
The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation
Koch, M. A., Tucker-Heard, G., Perdue, N. R., Killebrew, J. R., Urdahl, K. B., & Campbell, D. J. (2009) · Nature Immunology · doi:10.1038/ni.1731 · Cited by 1,258 · see citing works
Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells.
Battaglia, M., Stabilini, A., & Roncarolo, M. (2005) · Blood · doi:10.1182/blood-2004-10-3932 · Cited by 1,203 · see citing works
CTLA-4–Ig regulates tryptophan catabolism in vivo
Grohmann, U., Orabona, C., Fallarino, F., Vacca, C., Calcinaro, F., Falorni, A., Candeloro, P., Belladonna, M. L., Bianchi, R., Fioretti, M. C., et al. (2002) · Nature Immunology · doi:10.1038/ni846 · Cited by 1,160 · see citing works
The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2
Delgoffe, G. M., Pollizzi, K. N., Waickman, A. T., Heikamp, E., Meyers, D. J., Horton, M. R., Xiao, B., Worley, P. F., & Powell, J. D. (2011) · Nature Immunology · doi:10.1038/ni.2005 · Cited by 1,103 · see citing works
Active-Site Inhibitors of mTOR Target Rapamycin-Resistant Outputs of mTORC1 and mTORC2
Feldman, M. E., Apsel, B., Uotila, A., Loewith, R., Knight, Z. A., Ruggero, D., & Shokat, K. M. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000038 · Cited by 1,080 · see citing works
The Combined Effects of Tryptophan Starvation and Tryptophan Catabolites Down-Regulate T Cell Receptor ζ-Chain and Induce a Regulatory Phenotype in Naive T Cells
Fallarino, F., Grohmann, U., You, S., McGrath, B. C., Cavener, D. R., Vacca, C., Orabona, C., Bianchi, R., Belladonna, M. L., Volpi, C., et al. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.11.6752 · Cited by 1,042 · see citing works
Regulation and function of mTOR signalling in T cell fate decisions
Chi, H. (2012) · Nature Reviews Immunology · doi:10.1038/nri3198 · Cited by 1,035 · see citing works
Self-citation
Rapamycin passes the torch: a new generation of mTOR inhibitors
Benjamin, D., Colombi, M., Moroni, C., & Hall, M. N. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3531 · Cited by 981 · see citing works
Inhibition of Allogeneic T Cell Proliferation by Indoleamine 2,3-Dioxygenase–expressing Dendritic Cells
Terness, P., Bauer, T. M., Röse, L., Dufter, C., Watzlik, A., Simon, H., & Opelz, G. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20020052 · Cited by 939 · see citing works
IL-35-mediated induction of a potent regulatory T cell population
Collison, L. W., Chaturvedi, V., Henderson, A. L., Giacomin, P., Guy, C. S., Bankoti, J., Finkelstein, D., Forbes, K., Workman, C. J., Brown, S. A., et al. (2010) · Nature Immunology · doi:10.1038/ni.1952 · Cited by 870 · see citing works
Inflammatory T Cell Responses Rely on Amino Acid Transporter ASCT2 Facilitation of Glutamine Uptake and mTORC1 Kinase Activation
Nakaya, M., Xiao, Y., Zhou, X., Chang, J., Chang, M., Cheng, X., Blonska, M., Lin, X., & Sun, S. (2014) · Immunity · doi:10.1016/j.immuni.2014.04.007 · Cited by 870 · see citing works
T cell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR
Sauer, S., Bruno, L., Hertweck, A., Finlay, D. K., Leleu, M., Spivakov, M., Knight, Z. A., Cobb, B. S., Cantrell, D. A., O’Connor, E., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800928105 · Cited by 861 · see citing works
Glutamine Uptake and Metabolism Are Coordinately Regulated by ERK/MAPK during T Lymphocyte Activation
Carr, E. L., Kelman, A., Wu, G. S., Gopaul, R., Senkevitch, E., Aghvanyan, A., Turay, A. M., & Frauwirth, K. A. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903586 · Cited by 830 · see citing works
Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation
Choo, A. Y., Yoon, S.-O., Kim, S. G., Roux, P. P., & Blenis, J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809136105 · Cited by 813 · see citing works
Mechanisms of impaired regulation by CD4+CD25+FOXP3+ regulatory T cells in human autoimmune diseases
Buckner, J. H. (2010) · Nature reviews. Immunology · doi:10.1038/nri2889 · Cited by 790 · see citing works
mTORC1 couples immune signals and metabolic programming to establish Treg-cell function
Zeng, H., Yang, K., Cloer, C., Neale, G. A. M., Vogel, P., & Chi, H. (2013) · Nature · doi:10.1038/nature12297 · Cited by 789 · see citing works
Self-citation
Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism
Wan, X., Harkavy, B., Shen, N., Grohar, P. J., & Helman, L. J. (2006) · Oncogene · doi:10.1038/sj.onc.1209990 · Cited by 756 · see citing works
Rapamycin Promotes Expansion of Functional CD4+CD25+FOXP3+ Regulatory T Cells of Both Healthy Subjects and Type 1 Diabetic Patients
Battaglia, M., Stabilini, A., Migliavacca, B., Horejs‐Hoeck, J., Kaupper, T., & Roncarolo, M. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.12.8338 · Cited by 731 · see citing works
Regulatory T cells in cancer immunotherapy
Nishikawa, H., & Sakaguchi, S. (2014) · Current Opinion in Immunology · doi:10.1016/j.coi.2013.12.005 · Cited by 702 · see citing works
DNA demethylation in the human FOXP3 locus discriminates regulatory T cells from activated FOXP3+ conventional T cells
Baron, U., Floess, S., Wieczorek, G., Baumann, K., Grützkau, A., Dong, J., Thiel, A., Boeld, T. J., Hoffmann, P., Edinger, M., et al. (2007) · European Journal of Immunology · doi:10.1002/eji.200737594 · Cited by 694 · see citing works
The SLC3 and SLC7 families of amino acid transporters
Fotiadis, D., Kanai, Y., & Palacı́n, M. (2013) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.10.007 · Cited by 674 · see citing works
Cyclic adenosine monophosphate is a key component of regulatory T cell–mediated suppression
Bopp, T., Becker, C., Klein, M., Klein‐Hessling, S., Palmetshofer, A., Serfling, E., Heib, V., Becker, M., Kubach, J., Schmitt, S., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20062129 · Cited by 659 · see citing works
The mTOR Kinase Determines Effector versus Memory CD8+ T Cell Fate by Regulating the Expression of Transcription Factors T-bet and Eomesodermin
Rao, R. R., Li, Q., Odunsi, K., & Shrikant, P. A. (2010) · Immunity · doi:10.1016/j.immuni.2009.10.010 · Cited by 656 · see citing works
Neuropilin-1 distinguishes natural and inducible regulatory T cells among regulatory T cell subsets in vivo
Yadav, M., Louvet, C., Davini, D., Gardner, J. M., Martinez-Llordella, M., Bailey-Bucktrout, S., Anthony, B. A., Sverdrup, F. M., Head, R., Kuster, D. J., et al. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20120822 · Cited by 649 · see citing works
A Key Role of Leptin in the Control of Regulatory T Cell Proliferation
Rosa, V. D., Procaccini, C., Calı̀, G., Pirozzi, G., Fontana, S., Zappacosta, S., Cava, A. L., & Matarese, G. (2007) · Immunity · doi:10.1016/j.immuni.2007.01.011 · Cited by 637 · see citing works
Regulatory T cells: recommendations to simplify the nomenclature
Abbas, A. K., Benoist, C., Bluestone, J. A., Campbell, D. J., Ghosh, S., Hori, S., Jiang, S., Kuchroo, V. K., Mathis, D., Roncarolo, M. G., et al. (2013) · Nature Immunology · doi:10.1038/ni.2554 · Cited by 623 · see citing works
Neuropilin 1 is expressed on thymus-derived natural regulatory T cells, but not mucosa-generated induced Foxp3+ T reg cells
Weiss, J. M., Bilate, A. M., Gobert, M., Ding, Y., Curotto de Lafaille, M. A., Parkhurst, C. N., Xiong, H., Dolpady, J., Frey, A. B., Ruocco, M. G., et al. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20120914 · Cited by 621 · see citing works
PDK1 regulation of mTOR and hypoxia-inducible factor 1 integrate metabolism and migration of CD8+ T cells
Finlay, D. K., Rosenzweig, E., Sinclair, L. V., Feijoo-Carnero, C., Hukelmann, J. L., Rolf, J., Panteleyev, A. A., Okkenhaug, K., & Cantrell, D. A. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20112607 · Cited by 596 · see citing works
Antigen-dependent Proliferation of CD4+ CD25+ Regulatory T Cells In Vivo
Walker, L. S. K., Chodos, A. H., Eggena, M., Dooms, H., & Abbas, A. K. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030315 · Cited by 588 · see citing works
Stability and function of regulatory T cells is maintained by a neuropilin-1–semaphorin-4a axis
Delgoffe, G. M., Woo, S.-R., Turnis, M. E., Gravano, D. M., Guy, C., Overacre, A. E., Bettini, M. L., Vogel, P., Finkelstein, D., Bonnevier, J., et al. (2013) · Nature · doi:10.1038/nature12428 · Cited by 587 · see citing works
CD80 (B7-1) Binds Both CD28 and CTLA-4 with a Low Affinity and Very Fast Kinetics
van der Merwe, P. A., Bodian, D. L., Daenke, S., Linsley, P., & Davis, S. J. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.3.393 · Cited by 551 · see citing works
Foxo1 links homing and survival of naive T cells by regulating L-selectin, CCR7 and interleukin 7 receptor
Kerdiles, Y. M., Beisner, D. R., Tinoco, R., Dejean, A. S., Castrillón, D. H., DePinho, R. A., & Hedrick, S. Μ. (2009) · Nature Immunology · doi:10.1038/ni.1689 · Cited by 541 · see citing works
Cloning and Functional Characterization of a System ASC-like Na+-dependent Neutral Amino Acid Transporter
Utsunomiya‐Tate, N., Endou, H., & Kanai, Y. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.25.14883 · Cited by 532 · see citing works
The good, the bad and the ugly — TFH cells in human health and disease
Tangye, S. G., Ma, C. S., Brink, R. A., & Deenick, E. K. (2013) · Nature reviews. Immunology · doi:10.1038/nri3447 · Cited by 527 · see citing works
Adoptive T Cell Transfer for Cancer Immunotherapy in the Era of Synthetic Biology
Kalos, M. D., & June, C. H. (2013) · Immunity · doi:10.1016/j.immuni.2013.07.002 · Cited by 486 · see citing works
Essential role for CD103 in the T cell–mediated regulation of experimental colitis
Annacker, O., Coombes, J. L., Malmström, V., Uhlig, H. H., Bourne, T., Johansson‐Lindbom, B., Agace, W. W., Parker, C. M., & Powrie, F. M. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20040662 · Cited by 483 · see citing works
Normal T cell homeostasis: the conversion of naive cells into memory-phenotype cells
Sprent, J., & Surh, C. D. (2011) · Nature Immunology · doi:10.1038/ni.2018 · Cited by 480 · see citing works
T Regulatory and Primed Uncommitted CD4 T Cells Express CD73, Which Suppresses Effector CD4 T Cells by Converting 5′-Adenosine Monophosphate to Adenosine
Kobie, J. J., Shah, P. R., Li, Y., Rebhahn, J. A., Fowell, D. J., & Mosmann, T. R. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.10.6780 · Cited by 467 · see citing works
Mammalian Target of Rapamycin Protein Complex 2 Regulates Differentiation of Th1 and Th2 Cell Subsets via Distinct Signaling Pathways
Lee, K., Gudapati, P., Dragovic, S. M., Spencer, C. T., Joyce, S., Killeen, N. P., Magnuson, M. A., & Boothby, M. R. (2010) · Immunity · doi:10.1016/j.immuni.2010.06.002 · Cited by 464 · see citing works
Genetic Dissection of the Oncogenic mTOR Pathway Reveals Druggable Addiction to Translational Control via 4EBP-eIF4E
Hsieh, A. C., Costa, M. D., Zollo, O., Davis, C. B., Feldman, M. E., Testa, J. R., Meyuhas, O., Shokat, K. M., & Ruggero, D. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.01.021 · Cited by 464 · see citing works
Metabolic checkpoints in activated T cells
Wang, R., & Green, D. R. (2012) · Nature Immunology · doi:10.1038/ni.2386 · Cited by 457 · see citing works
Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases
Apsel, B., Blair, J. A., González, B., Nazif, T. M., Feldman, M. E., Aizenstein, B., Hoffman, R., Williams, R. L., Shokat, K. M., & Knight, Z. A. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.117 · Cited by 452 · see citing works
Cancer immunotherapy strategies based on overcoming barriers within the tumor microenvironment
Gajewski, T. F., Woo, S., Zha, Y., Spaapen, R. M., Zheng, Y., Corrales, L. P., & Spranger, S. (2013) · Current Opinion in Immunology · doi:10.1016/j.coi.2013.02.009 · Cited by 420 · see citing works
Differential impact of mammalian target of rapamycin inhibition on CD4 +CD25+Foxp3+ regulatory T cells compared with conventional CD4+ T cells
Zeiser, R., Leveson-Gower, D. B., Zambricki, E. A., Kambham, N., Beilhack, A., Loh, J., Hou, J.-Z., & Negrin, R. S. (2008) · Blood · doi:10.1182/blood-2007-06-094482 · Cited by 402 · see citing works
Phosphatidylinositol-3-OH kinase and nutrient-sensing mTOR pathways control T lymphocyte trafficking
Sinclair, L. V., Finlay, D. K., Feijóo, C. G., Cornish, G. H., Gray, A., Ager, A., Okkenhaug, K., Hagenbeek, T. J., Spits, H., & Cantrell, D. A. (2008) · Nature Immunology · doi:10.1038/ni.1603 · Cited by 391 · see citing works
T Cell Exit from Quiescence and Differentiation into Th2 Cells Depend on Raptor-mTORC1-Mediated Metabolic Reprogramming
Yang, K., Shrestha, S., Zeng, H., Karmaus, P. W. F., Neale, G. A. M., Vogel, P., Guertin, D. A., Lamb, R. F., & Chi, H. (2013) · Immunity · doi:10.1016/j.immuni.2013.09.015 · Cited by 389 · see citing works
Self-citation
Helios Expression Is a Marker of T Cell Activation and Proliferation
Akimova, T., Beier, U. H., Wang, L., Levine, M. H., & Hancock, W. W. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024226 · Cited by 389 · see citing works
An Oscillatory Switch in mTOR Kinase Activity Sets Regulatory T Cell Responsiveness
Procaccini, C., Rosa, V. D., Galgani, M., Abanni, L., Calı̀, G., Porcellini, A., Carbone, F., Fontana, S., Horváth, T. L., Cava, A. L., et al. (2010) · Immunity · doi:10.1016/j.immuni.2010.11.024 · Cited by 368 · see citing works
Foxp3-dependent and -independent molecules specific for CD25+CD4+ natural regulatory T cells revealed by DNA microarray analysis
Sugimoto, N., Oida, T., Hirota, K., Nakamura, K., Nomura, T., Uchiyama, T., & Sakaguchi, S. (2006) · International Immunology · doi:10.1093/intimm/dxl060 · Cited by 361 · see citing works
The receptor S1P1 overrides regulatory T cell-mediated immune suppression through Akt-mTOR
Liu, G., Burns, S., Huang, G., Boyd, K., Proia, R. L., Flavell, R. A., & Chi, H. (2009) · Nature Immunology · doi:10.1038/ni.1743 · Cited by 339 · see citing works
Self-citation
Infectious tolerance via the consumption of essential amino acids and mTOR signaling
Cobbold, S. P., Adams, E., Farquhar, C. A., Nolan, K. F., Howie, D., Lui, K. O., Fairchild, P. J., Mellor, A. L., Ron, D., & Waldmann, H. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903919106 · Cited by 336 · see citing works
Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor
Janes, M. R., Limon, J. J., So, L., Chen, J., Lim, R. J., Chavez, M. A., Vu, C., Lilly, M. B., Mallya, S., Ong, S. T., et al. (2010) · Nature Medicine · doi:10.1038/nm.2091 · Cited by 335 · see citing works
The S1P1-mTOR axis directs the reciprocal differentiation of TH1 and Treg cells
Liu, G., Yang, K., Burns, S., Shrestha, S., & Chi, H. (2010) · Nature Immunology · doi:10.1038/ni.1939 · Cited by 324 · see citing works
Self-citation
PI3K-Akt-mTORC1-S6K1/2 Axis Controls Th17 Differentiation by Regulating Gfi1 Expression and Nuclear Translocation of RORγ
Kurebayashi, Y., Nagai, S., Ikejiri, A., Ohtani, M., Ichiyama, K., Baba, Y., Yamada, T., Egami, S., Hoshii, T., Hirao, A., et al. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.02.007 · Cited by 323 · see citing works
A Role for CD103 in the Retention of CD4+CD25+ Treg and Control of Leishmania major Infection
Suffia, I., Reckling, S. K., Salay, G., & Belkaid, Y. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.9.5444 · Cited by 315 · see citing works
Expression of Helios in Peripherally Induced Foxp3+ Regulatory T Cells
Gottschalk, R. A., Corse, E., & Allison, J. P. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1102964 · Cited by 310 · see citing works
The tumor suppressor Tsc1 enforces quiescence of naive T cells to promote immune homeostasis and function
Yang, K., Neale, G. A. M., Green, D. R., He, W., & Chi, H. (2011) · Nature Immunology · doi:10.1038/ni.2068 · Cited by 291 · see citing works
Self-citation
Anergic T Cells Are Metabolically Anergic
Zheng, Y., Delgoffe, G. M., Meyer, C. F., Chan, W., & Powell, J. D. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0803510 · Cited by 280 · see citing works
Rapamycin inhibits differentiation of Th17 cells and promotes generation of FoxP3+ T regulatory cells
Kopf, H., de la Rosa, G. M., Howard, O. M. Z., & Chen, X. (2007) · International Immunopharmacology · doi:10.1016/j.intimp.2007.08.027 · Cited by 271 · see citing works
Contrasting Effects of Cyclosporine and Rapamycin in De Novo Generation of Alloantigen-Specific Regulatory T Cells
Gao, W., Lu, Y., Essawy, B. E., Oukka, M., Kuchroo, V. K., & Strom, T. B. (2007) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2007.01842.x · Cited by 260 · see citing works
A role for the transcription factor Helios in human CD4+CD25+ regulatory T cells
Getnet, D., Grosso, J. F., Goldberg, M. V., Harris, T., Yen, H., Bruno, T. C., Durham, N. M., Hipkiss, E. L., Pyle, K. J., & Wada, S. (2010) · Molecular Immunology · doi:10.1016/j.molimm.2010.02.001 · Cited by 248 · see citing works
The liver kinase B1 is a central regulator of T cell development, activation, and metabolism
MacIver, N. J., Blagih, J., Saucillo, D. C., Tonelli, L., Griss, T., Rathmell, J. C., & Jones, R. G. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100367 · Cited by 235 · see citing works
mTOR SignalingPreprint
Laplante, M., & Sabatini, D. M. (2011) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a011593 · Cited by 235 · see citing works
Regulation of CD4 T cell activation and effector function by inducible costimulator (ICOS)
Simpson, T. R., Quezada, S. A., & Allison, J. P. (2010) · Current Opinion in Immunology · doi:10.1016/j.coi.2010.01.001 · Cited by 234 · see citing works
IL-2 therapy promotes suppressive ICOS+ Treg expansion in melanoma patients
Sim, G. C., Martín‐Orozco, N., Jin, L., Yang, Y., Wu, S., Washington, E., Sanders, D., Lacey, C., Wang, Y., Vence, L. M., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci46266 · Cited by 231 · see citing works
Metabolism, migration and memory in cytotoxic T cells
Finlay, D. K., & Cantrell, D. A. (2011) · Nature reviews. Immunology · doi:10.1038/nri2888 · Cited by 220 · see citing works
Regulatory T cell proliferative potential is impaired in human autoimmune disease
Carbone, F., Rosa, V. D., Carrieri, P. B., Montella, S., Bruzzese, D., Porcellini, A., Procaccini, C., Cava, A. L., & Matarese, G. (2013) · Nature Medicine · doi:10.1038/nm.3411 · Cited by 214 · see citing works
Rapamycin-Mediated Enrichment of T Cells with Regulatory Activity in Stimulated CD4+ T Cell Cultures Is Not Due to the Selective Expansion of Naturally Occurring Regulatory T Cells but to the Induction of Regulatory Functions in Conventional CD4+ T Cells
Valmori, D., Tosello, V., Souleimanian, N. E., Godefroy, E., Scotto, L., Wang, Y., & Ayyoub, M. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.2.944 · Cited by 196 · see citing works
Cell-autonomous and -non-autonomous roles of CTLA-4 in immune regulation
Wing, K., Yamaguchi, T., & Sakaguchi, S. (2011) · Trends in Immunology · doi:10.1016/j.it.2011.06.002 · Cited by 184 · see citing works
Human T follicular helper (Tfh) cells and disease
Ma, C. S., & Deenick, E. K. (2013) · Immunology and Cell Biology · doi:10.1038/icb.2013.55 · Cited by 184 · see citing works
Regulatory T Cells as Immunotherapy
Singer, B. D., King, L. S., & D’Alessio, F. R. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00046 · Cited by 181 · see citing works
Regulatory T cell subsets in human cancer: are they regulating for or against tumor progression?
Whiteside, T. L. (2013) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-013-1490-y · Cited by 170 · see citing works
Promotion and prevention of autoimmune disease by CD8+ T cells
Gravano, D. M., & Hoyer, K. K. (2013) · Journal of Autoimmunity · doi:10.1016/j.jaut.2013.06.004 · Cited by 166 · see citing works
A Central Role for mTOR Kinase in Homeostatic Proliferation Induced CD8+ T Cell Memory and Tumor Immunity
Li, Q., Rao, R. R., Araki, K., Pollizzi, K. N., Odunsi, K. O., Powell, J. D., & Shrikant, P. A. (2011) · Immunity · doi:10.1016/j.immuni.2011.04.006 · Cited by 160 · see citing works
Phenotypic and Functional Properties of Helios+ Regulatory T Cells
Zabransky, D. J., Nirschl, C. J., Durham, N. M., Park, B. V., Ceccato, C. M., Bruno, T. C., Tam, A. J., Getnet, D., & Drake, C. G. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034547 · Cited by 160 · see citing works
Advances in distinguishing natural from induced Foxp3(+) regulatory T cells.
Lin, X.-H., Chen, M., Liu, Y., Guo, Z., He, X., Brand, D. D., & Zheng, S. G. (2013) · PubMed Central · Cited by 140 · see citing works
TSC1 regulates the balance between effector and regulatory T cells
Park, Y., Jin, H., Lopez, J. M., Elly, C., Kim, G., Murai, M., Kronenberg, M., & Liu, Y. (2013) · Journal of Clinical Investigation · doi:10.1172/jci69751 · Cited by 140 · see citing works
Akt1 and Akt2 are required for αβ thymocyte survival and differentiation
Juntilla, M. M., Wofford, J. A., Birnbaum, M. J., Rathmell, J. C., & Koretzky, G. A. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705285104 · Cited by 136 · see citing works
Leptin-Induced mTOR Activation Defines a Specific Molecular and Transcriptional Signature Controlling CD4+ Effector T Cell Responses
Procaccini, C., Rosa, V. D., Galgani, M., Carbone, F., Cassano, S., Greco, D., Qian, K., Auvinen, P., Calı̀, G., Stallone, G., et al. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1200935 · Cited by 136 · see citing works
CD28 Controls Differentiation of Regulatory T Cells from Naive CD4 T Cells
Guo, F., Iclozan, C., Suh, W., Anasetti, C., & Yu, X. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.4.2285 · Cited by 125 · see citing works
De novo induction of antigen-specific CD4+CD25+Foxp3+ regulatory T cells in vivo following systemic antigen administration accompanied by blockade of mTOR
Kang, J., Huddleston, S. J., Fraser, J. M., & Khoruts, A. (2008) · Journal of Leukocyte Biology · doi:10.1189/jlb.1207851 · Cited by 124 · see citing works
Retinoic Acid and Rapamycin Differentially Affect and Synergistically Promote the Ex Vivo Expansion of Natural Human T Regulatory Cells
Golovina, T. N., Mikheeva, T., Brusko, T. M., Blazar, B. R., Bluestone, J. A., & Riley, J. L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0015868 · Cited by 122 · see citing works
Aptamer-targeted inhibition of mTOR in T cells enhances antitumor immunity
Berezhnoy, A., Castro, I., Levay, A. K., Malek, T. R., & Gilboa, E. (2013) · Journal of Clinical Investigation · doi:10.1172/jci69856 · Cited by 121 · see citing works
Vital roles of mTOR complex 2 in Notch-driven thymocyte differentiation and leukemia
Lee, K., Nam, K. T., Cho, S. H., Gudapati, P., Hwang, Y., Park, D., Potter, R. M., Chen, J., Volanakis, E. J., & Boothby, M. R. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20111470 · Cited by 120 · see citing works
mTOR and metabolic pathways in T cell quiescence and functional activation
Yang, K., & Chi, H. (2012) · Seminars in Immunology · doi:10.1016/j.smim.2012.12.004 · Cited by 115 · see citing works
Self-citation
CD103 is a hallmark of tumor‐infiltrating regulatory T cells
Anz, D., Mueller, W., Golić, M., Kunz, W. G., Rapp, M., Koelzer, V. H., Ellermeier, J., Ellwart, J. W., Schnurr, M. M., Bourquin, C., et al. (2011) · International Journal of Cancer · doi:10.1002/ijc.25902 · Cited by 114 · see citing works
Cutting Edge: Rapamycin Augments Pathogen-Specific but Not Graft-Reactive CD8+ T Cell Responses
Ferrer, I. R., Wagener, M. E., Robertson, J. M., Turner, A., Araki, K., Ahmed, R., Kirk, A. D., Larsen, C. P., & Ford, M. L. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001176 · Cited by 111 · see citing works
Temsirolimus, an mTOR inhibitor, enhances anti-tumour effects of heat shock protein cancer vaccines
Wang, Y., Wang, X.-Y., Subjeck, J. R., Shrikant, P., & Kim, H. L. (2011) · British Journal of Cancer · doi:10.1038/bjc.2011.15 · Cited by 110 · see citing works
mTOR and lymphocyte metabolism
Zeng, H., & Chi, H. (2013) · Current Opinion in Immunology · doi:10.1016/j.coi.2013.05.002 · Cited by 101 · see citing works
Self-citation
Sirolimus Enhances the Magnitude and Quality of Viral-Specific CD8+ T-Cell Responses to Vaccinia Virus Vaccination in Rhesus Macaques
Turner, A. P., Shaffer, V. O., Araki, K., Martens, C. L., Turner, P. L., Gangappa, S., Ford, M. L., Ahmed, R., Kirk, A. D., & Larsen, C. P. (2011) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2010.03407.x · Cited by 100 · see citing works
Unequal Contribution of Akt Isoforms in the Double-Negative to Double-Positive Thymocyte Transition
Mao, C., Tili, E., Dose, M., Haks, M. C., Bear, S. E., Maroulakou, I. G., Horie, K., Gaitanaris, G., Fidanza, V., Ludwig, T. E., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.9.5443 · Cited by 100 · see citing works
AMP‐activated protein kinase regulates lymphocyte responses to metabolic stress but is largely dispensable for immune cell development and function
Mayer, A., Denanglaire, S., Viollet, B., Léo, O., & Andris, F. (2008) · European Journal of Immunology · doi:10.1002/eji.200738045 · Cited by 98 · see citing works
Immune System Dysfunction and Autoimmune Disease in Mice Lacking Emk (Par-1) Protein Kinase
Hurov, J., Stappenbeck, T. S., Zmasek, C. M., White, L. S., Ranganath, S. H., Russell, J. H., Chan, A. C., MURPHY, K. M. M., & Piwnica-Worms, H. M. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.9.3206-3219.2001 · Cited by 97 · see citing works
LKB1 is essential for the proliferation of T‐cell progenitors and mature peripheral T cells
Tamás, P., Macintyre, A., Finlay, D., Clarke, R., Feijoo‐Carnero, C., Ashworth, A., & Cantrell, D. (2010) · European Journal of Immunology · doi:10.1002/eji.200939677 · Cited by 94 · see citing works
Stability of human rapamycin-expanded CD4+CD25+ T regulatory cells
Tresoldi, E., Dell'Albani, I., Stabilini, A., Jofra, T., Valle, A., Gagliani, N., Bondanza, A., Roncarolo, M., & Battaglia, M. (2011) · Haematologica · doi:10.3324/haematol.2011.041483 · Cited by 92 · see citing works
Regulation of T‐cell survival and mitochondrial homeostasis by TSC1
O'Brien, T. F., Gorentla, B. K., Xie, D., Srivatsan, S., McLeod, I. X., He, Y.-W., & Zhong, X. (2011) · European Journal of Immunology · doi:10.1002/eji.201141411 · Cited by 86 · see citing works
Loss of T Cell CD98 H Chain Specifically Ablates T Cell Clonal Expansion and Protects from Autoimmunity
Cantor, J. M., Slepak, M., Ege, N., Chang, J. T., & Ginsberg, M. H. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100002 · Cited by 85 · see citing works
Distinct roles for PTEN in prevention of T cell lymphoma and autoimmunity in mice
Liu, X., Karnell, J. L., Yin, B., Zhang, R., Zhang, J., Li, P., Choi, Y., Maltzman, J. S., Pear, W. S., Bassing, C. H., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci42382 · Cited by 83 · see citing works
Helios Is Associated with CD4 T Cells Differentiating to T Helper 2 and Follicular Helper T Cells In Vivo Independently of Foxp3 Expression
Serre, K., Bénézech, C., Desanti, G. E., Bobat, S., Toellner, K., Bird, R., Chan, S. H., Kastner, P., Cunningham, A. F., MacLennan, I. C. M., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020731 · Cited by 83 · see citing works
The Tuberous Sclerosis Complex–Mammalian Target of Rapamycin Pathway Maintains the Quiescence and Survival of Naive T Cells
Wu, Q., Liu, Y., Chen, C., Ikenoue, T., Qiao, Y., Li, C.-S., Li, W., Guan, K., Liu, Y., & Zheng, P. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003968 · Cited by 82 · see citing works
Leptin Modulates the Survival of Autoreactive CD4+ T Cells through the Nutrient/Energy-Sensing Mammalian Target of Rapamycin Signaling Pathway
Galgani, M., Procaccini, C., Rosa, V. D., Carbone, F., Chieffi, P., Cava, A. L., & Matarese, G. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001674 · Cited by 80 · see citing works
The serine/threonine kinase LKB1 controls thymocyte survival through regulation of AMPK activation and Bcl-XL expression
Cao, Y., Li, H., Liu, H., Zheng, C., Ji, H., & Liu, X. (2009) · Cell Research · doi:10.1038/cr.2009.141 · Cited by 75 · see citing works
Phosphoinositide-dependent kinase 1 controls migration and malignant transformation but not cell growth and proliferation in PTEN-null lymphocytes
Finlay, D. K., Sinclair, L. V., Feijóo, C. G., Waugh, C. M., Hagenbeek, T. J., Spits, H., & Cantrell, D. A. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20090219 · Cited by 73 · see citing works
Suppression of leukemia development caused by PTEN loss
Guo, W., Schubbert, S., Chen, J. Y., Valamehr, B. B., Mosessian, S., Shi, H., Dang, N. H., Garcia, C., Theodoro, M. F., Varella‐Garcia, M., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1006937108 · Cited by 70 · see citing works
T-bet Controls Pathogenicity of CTLs in the Heart by Separable Effects on Migration and Effector Activity
Taqueti, V. R., Grabie, N., Colvin, R. A., Pang, H. B., Jarolı́m, P., Luster, A. D., Glimcher, L. H., & Lichtman, A. H. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.9.5890 · Cited by 66 · see citing works
Rasgrp1 mutation increases naïve T-cell CD44 expression and drives mTOR-dependent accumulation of Helios+ T cells and autoantibodies
Daley, S. R., Coakley, K. M., Hu, D. Y., Randall, K. L., Jenne, C. N., Limnander, A., Myers, D. R., Polakos, N. K., Enders, A., Roots, C. M., et al. (2013) · eLife · doi:10.7554/elife.01020 · Cited by 65 · see citing works
Loss of mTOR complex 1 induces developmental blockage in early T-lymphopoiesis and eradicates T-cell acute lymphoblastic leukemia cells
Hoshii, T., Kasada, A., Hatakeyama, T., Ohtani, M., Tadokoro, Y., Naka, K., Ikenoue, T., Ikawa, T., Kawamoto, H., Fehling, H. J., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1320265111 · Cited by 63 · see citing works
Molecular Determinants of Regulatory T Cell Development: The Essential Roles of Epigenetic Changes
Kitagawa, Y., Ohkura, N., & Sakaguchi, S. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00106 · Cited by 61 · see citing works
Rapamycin, unlike cyclosporine A, enhances suppressive functions of in vitro-induced CD4+CD25+ Tregs
Bocian, K., Borysowski, J., Wierzbicki, P., Wyzgał, J., Kłosowska, D., Białoszewska, A., Pączek, L., Górski, A., & Korczak-Kowalska, G. (2009) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfp586 · Cited by 59 · see citing works
TSC1/2 Signaling Complex Is Essential for Peripheral Naïve CD8+ T Cell Survival and Homeostasis in Mice
Zhang, L., Zhang, H., Li, L., Xiao, Y., Rao, E., Miao, Z., Chen, H., Sun, L., Li, H., Liu, G., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030592 · Cited by 54 · see citing works
Regulatory T Cells Exhibit Decreased Proliferation but Enhanced Suppression After Pulsing With Sirolimus
Singh, K., Kozyr, N. L., Stempora, L., Kirk, A. D., Larsen, C. P., Blazar, B. R., & Kean, L. S. (2012) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2011.03963.x · Cited by 49 · see citing works
The role of natural regulatory T cells in infection
Sanchez, A. M., & Yang, Y. (2010) · Immunologic Research · doi:10.1007/s12026-010-8176-8 · Cited by 43 · see citing works
Foxp3+ T Cells Inhibit Antitumor Immune Memory Modulated by mTOR Inhibition
Wang, Y., Sparwasser, T. D., Figlin, R. A., & Kim, H. L. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-2928 · Cited by 40 · see citing works
The Pten/PI3K pathway governs the homeostasis of Vα14iNKT cells
Kishimoto, H., Ohteki, T., Yajima, N., et al. (2006) · Blood · doi:10.1182/blood-2006-07-038059 · Cited by 39 · see citing works
Amino Acids Fuel T Cell-Mediated Inflammation
Poffenberger, M. C., & Jones, R. G. (2014) · Immunity · doi:10.1016/j.immuni.2014.04.017 · Cited by 36 · see citing works

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Authors: Chapman, N. M., & Chi, H.
Affiliations: St. Jude Children's Research Hospital (US)
ORCID: Chapman, Nicole M
Chi, Hongbo
Venue: Immunotherapy
Publisher: Informa UK Limited
Published: 2014-12
Volume: 6
Issue: 12
Pages: 1295-1311
ISSN: 1750-743X (ISSN-L)
1750-7448
DOI: 10.2217/imt.14.84
PMC: PMC4291176
OpenAlex: W2139896257
Cited by: 148
References: 139
Citations by year: 2026: 14 · 2025: 16 · 2024: 9 · 2023: 14 · 2022: 18 · 2021: 16 · 2020: 18 · 2019: 11 · 2018: 13 · 2017: 5 · 2016: 12 · 2015: 2
FWCI: 0.62
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Immunotherapy (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: US NIH ((AI101407, AI105887, CA176624 and NS064599),)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords: mTOR signaling, Foxp3+ regulatory T cells, mTORC1, mTORC2, immune tolerance, immunosuppression, Treg differentiation, conventional T cells, T cell homeostasis, mTOR inhibition, immunomodulation, Treg-targeted therapy
MeSH terms: Animals, Autoimmune Diseases, Disease Models, Animal, Homeostasis, Humans, Immune Tolerance, Immunosuppression Therapy, Neoplasms, Signal Transduction, T-Lymphocytes, Regulatory, Forkhead Transcription Factors, Immunomodulation, TOR Serine-Threonine Kinases, Molecular Targeted Therapy

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mTOR Signaling, Tregs and Immune Modulation

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