The Tumor Microenvironment Represses T Cell Mitochondrial Biogenesis to Drive Intratumoral T Cell Metabolic Insufficiency and Dysfunction

Scharping, Nicole E.; Menk, Ashley V.; Moreci, Rebecca S.; Whetstone, Ryan D.; Dadey, Rebekah E.; Watkins, Simon C.; Ferris, Robert L.; Delgoffe, Greg M.

doi:10.1016/j.immuni.2016.07.009

Cited by 848Cancer Immunotherapy and BiomarkersT-cell and B-cell ImmunologyImmune cells in cancer

The Tumor Microenvironment Represses T Cell Mitochondrial Biogenesis to Drive Intratumoral T Cell Metabolic Insufficiency and Dysfunction

Open access

Scharping, Nicole E., Menk, Ashley V., Moreci, Rebecca S., Whetstone, Ryan D., Dadey, Rebekah E., Watkins, Simon C., Ferris, Robert L., Delgoffe, Greg M.·2016·Immunity

DOI 10.1016/j.immuni.2016.07.009PMC PMC5207350

Open this paper in CoChat — free account Open PDF

Abstract

Although tumor-specific T cells recognize cancer cells, they are often rendered dysfunctional due to an immunosuppressive microenvironment. Here we showed that T cells demonstrated persistent loss of mitochondrial function and mass when infiltrating murine and human tumors, an effect specific to the tumor microenvironment and not merely caused by activation. Tumor-infiltrating T cells showed a progressive loss of PPAR-gamma coactivator 1α (PGC1α), which programs mitochondrial biogenesis, induced by chronic Akt signaling in tumor-specific T cells. Reprogramming tumor-specific T cells through enforced expression of PGC1α resulted in superior intratumoral metabolic and effector function. Our data support a model in which signals in the tumor microenvironment repress T cell oxidative metabolism, resulting in effector cells with metabolic needs that cannot be met. Our studies also suggest that modulation or reprogramming of the altered metabolism of tumor-infiltrating T cells might represent a potential strategy to reinvigorate dysfunctional T cells for cancer treatment.

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 · 10.1016/j.immuni.2016.07.009

Cites

44 of 44 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?

Exhausted T cells and tumor-infiltrating NK cells exhibit dysregulated mitochondrial biogenesis.
“Exhausted T cells and tumor-infiltrating NK cells also exhibit dysregulated mitochondrial biogenesis, a mechanism that has created interest in using strategies to improve mitochondrial biogenesis to promote tumor immunity (Scharping et al., 2016; Zheng et al., 2019).”
From Hallmarks of response, resistance, and toxicity to immune checkpoint blockade (2021) · cites this paper as Scharping et al., 2016

Self-check

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

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

Molecular and cellular insights into T cell exhaustion
Wherry, E. J., & Kurachi, M. (2015) · Nature Reviews Immunology · doi:10.1038/nri3862 · Cited by 4,652 · see citing works
Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression
Chang, C.-H., Qiu, J., O’Sullivan, D., Buck, M. D., Noguchi, T., Curtis, J. D., Chen, Q., Gindin, M., Gubin, M. M., van der Windt, G. J. W., et al. (2015) · Cell · doi:10.1016/j.cell.2015.08.016 · Cited by 3,331 · see citing works
Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice
Kim, J. M., Rasmussen, J. P., & Rudensky, A. Y. (2006) · Nature Immunology · doi:10.1038/ni1428 · Cited by 1,827 · see citing works
Mitochondria as sensors and regulators of calcium signalling
Rizzuto, R., De Stefani, D., Raffaello, A., & Mammucari, C. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3412 · Cited by 1,781 · see citing works
Immune Inhibitory Molecules LAG-3 and PD-1 Synergistically Regulate T-cell Function to Promote Tumoral Immune Escape
Woo, S.-R., Turnis, M. E., Goldberg, M. V., Bankoti, J., Selby, M., Nirschl, C. J., Bettini, M. L., Gravano, D. M., Vogel, P., Liu, C. L., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-1620 · Cited by 1,647 · see citing works
Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development
van der Windt, G. J. W., Everts, B., Chang, C.-H., Curtis, J. D., Freitas, T. C., Amiel, E., Pearce, E. J., & Pearce, E. L. (2012) · Immunity · doi:10.1016/j.immuni.2011.12.007 · Cited by 1,540 · see citing works
Phosphoenolpyruvate Is a Metabolic Checkpoint of Anti-tumor T Cell Responses
Ho, P.-C., Bihuniak, J. D., Macintyre, A. N., Staron, M., Liu, X., Amezquita, R., Tsui, Y.-C., Cui, G., Micevic, G., Perales, J. C., et al. (2015) · Cell · doi:10.1016/j.cell.2015.08.012 · Cited by 1,462 · see citing works
PGC-1 coactivators: inducible regulators of energy metabolism in health and disease
Finck, B. N. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27794 · Cited by 1,427 · see citing works
Fueling Immunity: Insights into Metabolism and Lymphocyte Function
Pearce, E. L., Poffenberger, M. C., Chang, C.-H., & Jones, R. G. (2013) · Science · doi:10.1126/science.1242454 · Cited by 1,363 · see citing works
Combination cancer immunotherapy and new immunomodulatory targets
Mahoney, K. M., Rennert, P. D., & Freeman, G. J. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4591 · Cited by 1,294 · see citing works
Regulation of pgc-1α, a nodal regulator of mitochondrial biogenesis
Fernandez-Marcos, P. J., & Auwerx, J. (2011) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.110.001917 · Cited by 1,237 · see citing works
Overcoming T cell exhaustion in infection and cancer
Pauken, K. E., & Wherry, E. J. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.02.008 · Cited by 1,177 · see citing works
T-cell exhaustion in the tumor microenvironment
Jiang, Y., Li, Y., & Zhu, B. (2015) · Cell Death and Disease · doi:10.1038/cddis.2015.162 · Cited by 1,151 · see citing works
Antagonistic crosstalk between NF-κB and SIRT1 in the regulation of inflammation and metabolic disorders
Kauppinen, A., Suuronen, T., Ojala, J. O., Kaarniranta, K., & Salminen, A. (2013) · Cellular Signalling · doi:10.1016/j.cellsig.2013.06.007 · Cited by 1,001 · see citing works
T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment
Crespo, J., Sun, H., Welling, T. H., Tian, Z., & Zou, W. (2013) · Current Opinion in Immunology · doi:10.1016/j.coi.2012.12.003 · Cited by 752 · see citing works
Tolerance and exhaustion: defining mechanisms of T cell dysfunction
Schietinger, A., & Greenberg, P. D. (2013) · Trends in Immunology · doi:10.1016/j.it.2013.10.001 · Cited by 676 · see citing works
Adaptive Immune Resistance: How Cancer Protects from Immune Attack
Ribas, A. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0563 · Cited by 619 · see citing works
CD8 memory T cells have a bioenergetic advantage that underlies their rapid recall ability
van der Windt, G. J. W., O’Sullivan, D., Everts, B., Huang, S. C.-C., Buck, M. D., Curtis, J. D., Chang, C.-H., Smith, A. M., Ai, T., Faubert, B., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1221740110 · Cited by 523 · see citing works
Genetic absence of PD-1 promotes accumulation of terminally differentiated exhausted CD8+ T cells
Odorizzi, P. M., Pauken, K. E., Paley, M., Sharpe, A. H., & Wherry, E. J. (2015) · The Journal of Experimental Medicine · doi:10.1084/jem.20142237 · Cited by 470 · see citing works
mTORC1 and mTORC2 selectively regulate CD8+ T cell differentiation
Pollizzi, K. N., Patel, C. H., Sun, I., Oh, M. H., Waickman, A. T., Wen, J., Delgoffe, G. M., & Powell, J. D. (2015) · Journal of Clinical Investigation · doi:10.1172/jci77746 · Cited by 409 · see citing works
Self-citation
Cancer mediates effector T cell dysfunction by targeting microRNAs and EZH2 via glycolysis restriction
Zhao, E., Maj, T., Kryczek, I., Li, W., Wu, K., Zhao, L., Wei, S., Crespo, J., Wan, S., Vatan, L., et al. (2016) · Nature Immunology · doi:10.1038/ni.3313 · Cited by 405 · see citing works
Cytometric assessment of mitochondria using fluorescent probes
Cottet‐Rousselle, C., Ronot, X., Leverve, X. M., & Mayol, J. (2011) · Cytometry Part A · doi:10.1002/cyto.a.21061 · Cited by 402 · see citing works
Direct Coupling of Transcription and mRNA Processing through the Thermogenic Coactivator PGC-1
Monsalve, M., Wu, Z., Adelmant, G., Puigserver, P., Fan, M., & Spiegelman, B. M. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00031-9 · Cited by 395 · see citing works
Mitochondrial Membrane Potential Identifies Cells with Enhanced Stemness for Cellular Therapy
Sukumar, M., Liu, J., Mehta, G. U., Patel, S. J., Roychoudhuri, R., Crompton, J. G., Klebanoff, C. A., Ji, Y., Li, P., Yu, Z., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.11.002 · Cited by 391 · see citing works
The Transcription Factor FoxO1 Sustains Expression of the Inhibitory Receptor PD-1 and Survival of Antiviral CD8+ T Cells during Chronic Infection
Staron, M. M., Gray, S. M., Marshall, H. D., Parish, I. A., Chen, J. H., Perry, C. J., Cui, G., Li, M. O., & Kaech, S. M. (2014) · Immunity · doi:10.1016/j.immuni.2014.10.013 · Cited by 384 · see citing works
Akt Inhibition Enhances Expansion of Potent Tumor-Specific Lymphocytes with Memory Cell Characteristics
Crompton, J. G., Sukumar, M., Roychoudhuri, R., Clever, D. C., Gros, A., Eil, R. L., Tran, E., Hanada, K., Yu, Z., Palmer, D. C., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-2277 · Cited by 343 · see citing works
T cell metabolic fitness in antitumor immunity
Siska, P. J., & Rathmell, J. C. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.02.007 · Cited by 315 · see citing works
Changes in the carbohydrate metabolism of mitogenicellay stimulated human peripheral lymphocytes I. Stimulation by phytohaemagglutinin
Roos, D., & Loos, J. A. (1970) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/0304-4165(70)90182-0 · Cited by 296 · see citing works
Protein Kinase B Controls Transcriptional Programs that Direct Cytotoxic T Cell Fate but Is Dispensable for T Cell Metabolism
Macintyre, A. N., Finlay, D. K., Preston, G., Sinclair, L. V., Waugh, C. M., Tamas, P., Feijóo, C. G., Okkenhaug, K., & Cantrell, D. A. (2011) · Immunity · doi:10.1016/j.immuni.2011.01.012 · Cited by 274 · see citing works
Inhibitory Receptor Expression Depends More Dominantly on Differentiation and Activation than “Exhaustion” of Human CD8 T Cells
Legat, A., Speiser, D. E., Pircher, H., Zehn, D., & Marraco, S. A. F. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00455 · Cited by 250 · see citing works
Targeting regulatory T cells in tumors
Liu, C., Workman, C. J., & Vignali, D. A. A. (2016) · The FEBS Journal · doi:10.1111/febs.13656 · Cited by 228 · see citing works
Mutual Dependence of Foxo3a and PGC-1α in the Induction of Oxidative Stress Genes
Olmos, Y., Valle, I., Borniquel, S., Tiérrez, A., Soria, E., Lamas, S., & Monsalve, M. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m807397200 · Cited by 224 · see citing works
Immune Checkpoint Inhibitors: New Insights and Current Place in Cancer Therapy
La-Beck, N. M., Jean, G. W., Huynh, C., Alzghari, S. K., & Lowe, D. B. (2015) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.1643 · Cited by 217 · see citing works
Perturbations in Mitochondrial Dynamics Induced by Human Mutant PINK1 Can Be Rescued by the Mitochondrial Division Inhibitor mdivi-1
Cui, M., Tang, X., Christian, W. V., Yoon, Y., & Tieu, K. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.066662 · Cited by 205 · see citing works
The p65 subunit of NF-κB binds to PGC-1α, linking inflammation and metabolic disturbances in cardiac cells
Álvarez-Guardia, D., Palomer, X., Coll, T., Davidson, M. M., Chan, T. O., Feldman, A. M., Laguna, J. C., & Vázquez‐Carrera, M. (2010) · Cardiovascular Research · doi:10.1093/cvr/cvq080 · Cited by 187 · see citing works
TNF-α reduces PGC-1α expression through NF-κB and p38 MAPK leading to increased glucose oxidation in a human cardiac cell model
Palomer, X., Álvarez-Guardia, D., Rodríguez‐Calvo, R., Coll, T., Laguna, J. C., Davidson, M. M., Chan, T. O., Feldman, A. M., & Vázquez‐Carrera, M. (2008) · Cardiovascular Research · doi:10.1093/cvr/cvn327 · Cited by 178 · see citing works
Tumor necrosis factor and interleukin 1 decrease RXRα, PPARα, PPARγ, LXRα, and the coactivators SRC-1, PGC-1α, and PGC-1β in liver cells
Kim, M. S., Sweeney, T. R., Shigenaga, J. K., Chui, L. G., Moser, A., Grunfeld, C., & Feingold, K. R. (2007) · Metabolism · doi:10.1016/j.metabol.2006.10.007 · Cited by 168 · see citing works
Flow Cytometry-Based Assessment of Mitophagy Using MitoTracker
Xiao, B., Deng, X., Zhou, W., & Tan, E.-K. (2016) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2016.00076 · Cited by 121 · see citing works
Feeding an army: The metabolism of T cells in activation, anergy, and exhaustion
Delgoffe, G. M., & Powell, J. D. (2015) · Molecular Immunology · doi:10.1016/j.molimm.2015.07.026 · Cited by 83 · see citing works
Self-citation
Targeting mitochondria as a therapeutic target in cancer
Wenner, C. E. (2011) · Journal of Cellular Physiology · doi:10.1002/jcp.22788 · Cited by 82 · see citing works
Inactivation of Foxo3a and Subsequent Downregulation of PGC-1α Mediate Nitric Oxide-Induced Endothelial Cell Migration
Borniquel, S., García-Quintáns, N., Valle, I., Olmos, Y., Wild, B., Martínez‐Granero, F., Soria, E., Lamas, S., & Monsalve, M. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.00175-10 · Cited by 73 · see citing works
Caveolae-Dependent and -Independent Uptake of Albumin in Cultured Rodent Pulmonary Endothelial Cells
Li, H., Li, J., Wasserloos, K., Wallace, C. T., Sullivan, M., Bauer, P. M., Stolz, D. B., Lee, J. S., Watkins, S. C., Croix, C. M. S., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081903 · Cited by 65 · see citing works
Self-citation
Transcriptional Control of Energy Homeostasis through the PGC1 Coactivators
Spiegelman, B. M. (2007) · Novartis Foundation symposium · doi:10.1002/9780470985571.ch2 · Cited by 56 · see citing works
Interferon-beta affects mitochondrial activity in CD4 + lymphocytes: Implications for mechanism of action in multiple sclerosis
Haghikia, A., Faissner, S., Pappas, D. J., Puła, B., Akkad, D. A., Arning, L., Ruhrmann, S., Duscha, A., Gold, R., Baranzini, S. E., et al. (2014) · Multiple Sclerosis Journal · doi:10.1177/1352458514561909 · Cited by 16 · see citing works

Flagged first, then by citations

Research works printed but not linked: 1

Scarpulla RC Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 2011 1813 1269 1278 PMC3035754 20933024

Sorted by citations

CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer
McLane, L. M., Abdel-Hakeem, M. S., & Wherry, E. J. (2019) · Annual Review of Immunology · doi:10.1146/annurev-immunol-041015-055318 · Cited by 1,973 · see citing works
The diverse functions of the PD1 inhibitory pathway
Sharpe, A. H., & Pauken, K. E. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2017.108 · Cited by 1,977 · see citing works
Hallmarks of response, resistance, and toxicity to immune checkpoint blockade
Morad, G., Helmink, B. A., Sharma, P., & Wargo, J. A. (2021) · Cell · doi:10.1016/j.cell.2021.09.020 · Cited by 1,648 · see citing works
Metabolic support of tumour-infiltrating regulatory T cells by lactic acid
Watson, M. J., Vignali, P., Mullett, S. J., Overacre-Delgoffe, A. E., Peralta, R. M., Grebinoski, S., Menk, A. V., Rittenhouse, N., DePeaux, K., Whetstone, R. D., et al. (2021) · Nature · doi:10.1038/s41586-020-03045-2 · Cited by 1,280 · see citing works
Self-citation
Metabolic Instruction of Immunity
Buck, M. D., Sowell, R., Kaech, S. M., & Pearce, E. L. (2017) · Cell · doi:10.1016/j.cell.2017.04.004 · Cited by 1,232 · see citing works
Mitochondria are the powerhouses of immunity
Mills, E. L., Kelly, B., & O'Neill, L. A. J. (2017) · Nature Immunology · doi:10.1038/ni.3704 · Cited by 1,161 · see citing works
Turning Cold into Hot: Firing up the Tumor Microenvironment
Duan, Q., Zhang, H., Zheng, J., & Zhang, L. (2020) · Trends in Cancer · doi:10.1016/j.trecan.2020.02.022 · Cited by 934 · see citing works
Mitochondrial stress induced by continuous stimulation under hypoxia rapidly drives T cell exhaustion
Scharping, N. E., Rivadeneira, D. B., Menk, A. V., Vignali, P. D. A., Ford, B. R., Rittenhouse, N. L., Peralta, R., Wang, Y., Wang, Y., DePeaux, K., et al. (2021) · Nature Immunology · doi:10.1038/s41590-020-00834-9 · Cited by 897 · see citing works
Self-citation
Metabolism of immune cells in cancer
Leone, R. D., & Powell, J. D. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-020-0273-y · Cited by 877 · see citing works
Mitochondrial Metabolism as a Target for Cancer Therapy
Vasan, K., Werner, M., & Chandel, N. S. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.06.019 · Cited by 746 · see citing works
Navigating metabolic pathways to enhance antitumour immunity and immunotherapy
Li, X., Wenes, M., Romero, P. J., Huang, S. C., Fendt, S., & Ho, P. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0203-7 · Cited by 745 · see citing works
Obstacles Posed by the Tumor Microenvironment to T cell Activity: A Case for Synergistic Therapies
Anderson, K. G., Stromnes, I. M., & Greenberg, P. D. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.02.008 · Cited by 706 · see citing works
CAR immune cells: design principles, resistance and the next generation
Labanieh, L., & Mackall, C. (2023) · Nature · doi:10.1038/s41586-023-05707-3 · Cited by 606 · see citing works
Engineering CAR-T Cells for Next-Generation Cancer Therapy
Hong, M., Clubb, J. D., & Chen, Y. Y. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.07.005 · Cited by 644 · see citing works
CD8+ T cell metabolism in infection and cancer
Reina-Campos, M., Scharping, N. E., & Goldrath, A. W. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00537-8 · Cited by 574 · see citing works
Self-citation
The Roles of CD8+ T Cell Subsets in Antitumor Immunity
Paul, M. S., & Ohashi, P. S. (2020) · Trends in Cell Biology · doi:10.1016/j.tcb.2020.06.003 · Cited by 609 · see citing works
Metabolic barriers to cancer immunotherapy
DePeaux, K., & Delgoffe, G. M. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00541-y · Cited by 614 · see citing works
Self-citation
Disturbed mitochondrial dynamics in CD8+ TILs reinforce T cell exhaustion
Yu, Y.-R., Imrichova, H., Wang, H., Chao, T., Xiao, Z., Gao, M., Rincon-Restrepo, M., Franco, F., Genolet, R., Cheng, W.-C., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0793-3 · Cited by 593 · see citing works
Impaired mitochondrial oxidative phosphorylation limits the self-renewal of T cells exposed to persistent antigen
Vardhana, S. A., Hwee, M. A., Berisa, M., Wells, D. K., Yost, K. E., King, B., Smith, M., Herrera, P. S., Chang, H. Y., Satpathy, A. T., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0725-2 · Cited by 575 · see citing works
Metabolic Regulation of T Cell Longevity and Function in Tumor Immunotherapy
Kishton, R. J., Sukumar, M., & Restifo, N. P. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.06.016 · Cited by 548 · see citing works
Immune checkpoints and their inhibition in cancer and infectious diseases
Dyck, L., & Mills, K. H. G. (2017) · European Journal of Immunology · doi:10.1002/eji.201646875 · Cited by 541 · see citing works
Revisiting the PD-1 pathway
Patsoukis, N., Wang, Q., Strauss, L., & Boussiotis, V. A. (2020) · Science Advances · doi:10.1126/sciadv.abd2712 · Cited by 539 · see citing works
Roles of PD-1/PD-L1 Pathway: Signaling, Cancer, and Beyond
Ai, L., Xu, A., & Xu, J. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-981-15-3266-5_3 · Cited by 531 · see citing works
Efficacy of PD-1 Blockade Is Potentiated by Metformin-Induced Reduction of Tumor Hypoxia
Scharping, N. E., Menk, A. V., Whetstone, R. D., Zeng, X., & Delgoffe, G. M. (2017) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-16-0103 · Cited by 520 · see citing works
Self-citation
Early TCR Signaling Induces Rapid Aerobic Glycolysis Enabling Distinct Acute T Cell Effector Functions
Menk, A. V., Scharping, N. E., Moreci, R. S., Zeng, X., Guy, C. S., Salvatore, S. R., Bae, H. R., Xie, J., Young, H. A., Wendell, S. G., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.01.040 · Cited by 478 · see citing works
Self-citation
CD8+ T cells in the cancer-immunity cycle
Giles, J. R., Globig, A.-M., Kaech, S. M., & Wherry, E. J. (2023) · Immunity · doi:10.1016/j.immuni.2023.09.005 · Cited by 467 · see citing works
Targeted deletion of PD-1 in myeloid cells induces antitumor immunity
Strauss, L., Mahmoud, M. A. A., Weaver, J. D., Tijaro-Ovalle, N. M., Christofides, A., Wang, Q., Pal, R., Yuan, M., Asara, J., Patsoukis, N., et al. (2020) · Science Immunology · doi:10.1126/sciimmunol.aay1863 · Cited by 437 · see citing works
Role of tumor microenvironment in cancer progression and therapeutic strategy
Wang, Q., Shao, X., Zhang, Y., Zhu, M., Wang, F. X. C., Mu, J., Li, J., Yao, H., & Chen, K. (2023) · Cancer Medicine · doi:10.1002/cam4.5698 · Cited by 462 · see citing works
Programming CAR-T cells to kill cancer
Labanieh, L., Majzner, R. G., & Mackall, C. L. (2018) · Nature Biomedical Engineering · doi:10.1038/s41551-018-0235-9 · Cited by 438 · see citing works
IRE1α–XBP1 controls T cell function in ovarian cancer by regulating mitochondrial activity
Song, M., Sandoval, T. A., Chae, C.-S., Chopra, S., Tan, C., Rutkowski, M. R., Raundhal, M., Chaurio, R. A., Payne, K. K., Konrad, C., et al. (2018) · Nature · doi:10.1038/s41586-018-0597-x · Cited by 413 · see citing works
T‐cell exhaustion in HIV infection
Fenwick, C. W., Joo, V., Jacquier, P., Noto, A., Banga, R., Perreau, M., & Pantaleo, G. (2019) · Immunological Reviews · doi:10.1111/imr.12823 · Cited by 412 · see citing works
The spectrum of T cell metabolism in health and disease
Bantug, G. R., Galluzzi, L., Kroemer, G., & Hess, C. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2017.99 · Cited by 421 · see citing works
Mitochondrial activation chemicals synergize with surface receptor PD-1 blockade for T cell-dependent antitumor activity
Chamoto, K., Chowdhury, P. S., Kumar, A., Sonomura, K., Matsuda, F., Fagarasan, S., & Honjo, T. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1620433114 · Cited by 413 · see citing works
Energy metabolism in health and diseases
Liu, H., Wang, S., Wang, J., Guo, X., Song, Y., Fu, K., Gao, Z., Liu, D., He, W., & Yang, L. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02141-x · Cited by 438 · see citing works
Mitochondrial control of immunity: beyond ATP
Mehta, M., Weinberg, S. E., & Chandel, N. S. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2017.66 · Cited by 398 · see citing works
T Cell Exhaustion
Baessler, A., & Vignali, D. A. A. (2024) · Annual Review of Immunology · doi:10.1146/annurev-immunol-090222-110914 · Cited by 420 · see citing works
Mitochondrial dysregulation and glycolytic insufficiency functionally impair CD8 T cells infiltrating human renal cell carcinoma
Siska, P. J., Beckermann, K. E., Mason, F. M., Andrejeva, G., Greenplate, A. R., Sendor, A. B., Chiang, Y.-C. J., Corona, A. L., Gemta, L. F., Vincent, B. G., et al. (2017) · JCI Insight · doi:10.1172/jci.insight.93411 · Cited by 389 · see citing works
From bench to bed: the tumor immune microenvironment and current immunotherapeutic strategies for hepatocellular carcinoma
Fu, Y., Liu, S., Zeng, S., & Shen, H. (2019) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-019-1396-4 · Cited by 393 · see citing works
Exhaustion and senescence: two crucial dysfunctional states of T cells in the tumor microenvironment
Zhao, Y., Shao, Q., & Peng, G. (2020) · Cellular & Molecular Immunology · doi:10.1038/s41423-019-0344-8 · Cited by 382 · see citing works
Modulating Glycolysis to Improve Cancer Therapy
Chelakkot, C., Chelakkot, V. S., Shin, Y. K., & Song, K. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032606 · Cited by 378 · see citing works
Metabolic communication in the tumour–immune microenvironment
Kao, K., Vilbois, S., Tsai, C., & Ho, P. (2022) · Nature Cell Biology · doi:10.1038/s41556-022-01002-x · Cited by 354 · see citing works
Metabolism as a guiding force for immunity
Jung, J., Zeng, H., & Horng, T. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0217-x · Cited by 345 · see citing works
Accumulation of long-chain fatty acids in the tumor microenvironment drives dysfunction in intrapancreatic CD8+ T cells
Manzo, T., Prentice, B. M., Anderson, K. G., Raman, A. T., Schalck, A. P., Codreanu, G. S., Lauson, C. B. N., Tiberti, S., Raimondi, A., Jones, M. A., et al. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20191920 · Cited by 345 · see citing works
The tumor microenvironment as a metabolic barrier to effector T cells and immunotherapy
Lim, A. R., Rathmell, W. K., & Rathmell, J. C. (2020) · eLife · doi:10.7554/elife.55185 · Cited by 330 · see citing works
Immune evasion through mitochondrial transfer in the tumour microenvironment
Ikeda, H., Kawase, K., Nishi, T., Watanabe, T., Takenaga, K., Inozume, T., Ishino, T., Aki, S., Lin, J., Kawashima, S., et al. (2025) · Nature · doi:10.1038/s41586-024-08439-0 · Cited by 330 · see citing works
Proteomics of Melanoma Response to Immunotherapy Reveals Mitochondrial Dependence
Harel, M., Ortenberg, R., Varanasi, S. K., Mangalhara, K. C., Mardamshina, M., Markovits, E., Baruch, E. N., Tripple, V., Arama-Chayoth, M., Greenberg, E., et al. (2019) · Cell · doi:10.1016/j.cell.2019.08.012 · Cited by 323 · see citing works
4-1BB costimulation induces T cell mitochondrial function and biogenesis enabling cancer immunotherapeutic responses
Menk, A. V., Scharping, N. E., Rivadeneira, D. B., Calderon, M. J., Watson, M. J., Dunstane, D., Watkins, S. C., & Delgoffe, G. M. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20171068 · Cited by 313 · see citing works
Self-citation
Single-cell metabolic profiling of human cytotoxic T cells
Hartmann, F. J., Mrdjen, D., McCaffrey, E., Glass, D. R., Greenwald, N. F., Bharadwaj, A., Khair, Z., Verberk, S. G. S., Baranski, A., Baskar, R., et al. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0651-8 · Cited by 310 · see citing works
Metabolic flexibility determines human NK cell functional fate in the tumor microenvironment
Poznanski, S. M., Singh, K., Ritchie, T. M., Aguiar, J. A., Fan, I. Y., Portillo, A. L., Rojas, E. A. P., Vahedi, F., El‐Sayes, A., Xing, S., et al. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.03.023 · Cited by 309 · see citing works
Targeting metabolism to regulate immune responses in autoimmunity and cancer
Patel, C. H., Leone, R. D., Horton, M. R., & Powell, J. D. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0032-5 · Cited by 307 · see citing works
Metabolic adaptation of lymphocytes in immunity and disease
Chapman, N. M., & Chi, H.-B. (2022) · Immunity · doi:10.1016/j.immuni.2021.12.012 · Cited by 263 · see citing works
Linoleic acid potentiates CD8+ T cell metabolic fitness and antitumor immunity
Lauson, C. B. N., Tiberti, S., Corsetto, P. A., Conte, F., Tyagi, P., Machwirth, M., Ebert, S., Loffreda, A., Scheller, L., Sheta, D., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.02.013 · Cited by 294 · see citing works
Metabolic and Epigenetic Coordination of T Cell and Macrophage Immunity
Phan, A. T., Goldrath, A. W., & Glass, C. K. (2017) · Immunity · doi:10.1016/j.immuni.2017.04.016 · Cited by 291 · see citing works
Reprogramming lipid metabolism prevents effector T cell senescence and enhances tumor immunotherapy
Liu, X., Hartman, C. L., Li, L., Albert, C. J., Si, F., Gao, A., Huang, L. J., Zhao, Y., Lin, W., Hsueh, E. C., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.aaz6314 · Cited by 278 · see citing works
Inflammation: the incubator of the tumor microenvironment
Denk, D., & Greten, F. R. (2022) · Trends in cancer · doi:10.1016/j.trecan.2022.07.002 · Cited by 279 · see citing works
Germinal center B cells selectively oxidize fatty acids for energy while conducting minimal glycolysis
Weisel, F. J., Mullett, S. J., Elsner, R. A., Menk, A. V., Trivedi, N. H., Luo, W., Wikenheiser, D. J., Hawse, W. F., Chikina, M. D., Smita, S., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0598-4 · Cited by 274 · see citing works
Self-citation
CD38-NAD+Axis Regulates Immunotherapeutic Anti-Tumor T Cell Response
Chatterjee, S., Daenthanasanmak, A., Chakraborty, P., Wyatt, M. W., Dhar, P., Selvam, S. P., Fu, J., Zhang, J., Nguyen, H., Kang, I., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.10.006 · Cited by 270 · see citing works
Intercellular nanotube-mediated mitochondrial transfer enhances T cell metabolic fitness and antitumor efficacy
Baldwin, J., Heuser-Loy, C., Saha, T., Schelker, R. C., Slavkovic‐Lukic, D., Strieder, N., Hernandez-Lopez, I., Rana, N., Barden, M., Mastrogiovanni, F., et al. (2024) · Cell · doi:10.1016/j.cell.2024.08.029 · Cited by 266 · see citing works
An Overview: The Diversified Role of Mitochondria in Cancer Metabolism
Liu, Y., Sun, Y., Guo, Y., Shi, X., Chen, X., Feng, W., Wu, L., Zhang, J., Yu, S., Wang, Y., et al. (2023) · International Journal of Biological Sciences · doi:10.7150/ijbs.81609 · Cited by 260 · see citing works
The Transcription Factor Bhlhe40 Programs Mitochondrial Regulation of Resident CD8+ T Cell Fitness and Functionality
Li, C., Zhu, B., Son, Y. M., Wang, Z., Jiang, L., Xiang, M., Ye, Z., Beckermann, K. E., Wu, Y., Jenkins, J. W., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.08.013 · Cited by 244 · see citing works
Cellular networks controlling T cell persistence in adoptive cell therapy
Chan, J. D., Lai, J., Slaney, C. Y., Kallies, A., Beavis, P. A., & Darcy, P. K. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00539-6 · Cited by 242 · see citing works
RASA2 ablation in T cells boosts antigen sensitivity and long-term function
Carnevale, J. C., Shifrut, E., Kale, N., Nyberg, W. A., Blaeschke, F., Chen, Y. Y., Li, Z., Bapat, S. P., Diolaiti, M. E., O’Leary, P. C., et al. (2022) · Nature · doi:10.1038/s41586-022-05126-w · Cited by 236 · see citing works
Strategies to Address Chimeric Antigen Receptor Tonic Signaling
Ajina, A., & Maher, J. F. (2018) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-17-1097 · Cited by 238 · see citing works
Tumor cell oxidative metabolism as a barrier to PD-1 blockade immunotherapy in melanoma
Najjar, Y. G., Menk, A. V., Sander, C., Rao, U. N. M., Karunamurthy, A. D., Bhatia, R., Zhai, S., Kirkwood, J. M., & Delgoffe, G. M. (2019) · JCI Insight · doi:10.1172/jci.insight.124989 · Cited by 234 · see citing works
Self-citation
Fatty Acid Oxidation Controls CD8+ Tissue-Resident Memory T-cell Survival in Gastric Adenocarcinoma
Lin, R., Zhang, H., Yuan, Y., He, Q., Zhou, J., Li, S., Sun, Y., Li, D. Y., Qiu, H.-B., Wang, W., et al. (2020) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-19-0702 · Cited by 234 · see citing works
Targeting tumor microenvironment in ovarian cancer: Premise and promise
Jiang, Y., Wang, C., & Zhou, S. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188361 · Cited by 233 · see citing works
Hypoxic glioma-derived exosomes promote M2-like macrophage polarization by enhancing autophagy induction
Xu, J., Zhang, J., Zhang, Z., Gao, Z., Qi, Y., Qiu, W., Pan, Z., Guo, Q., Li, B., Zhao, S., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03664-1 · Cited by 226 · see citing works
Vaccine-boosted CAR T crosstalk with host immunity to reject tumors with antigen heterogeneity
Ma, L., Hostetler, A., Morgan, D. M., Maiorino, L., Sulkaj, I., Whittaker, C. A., Neeser, A., Pires, I. S., Yousefpour, P., Gregory, J. R., et al. (2023) · Cell · doi:10.1016/j.cell.2023.06.002 · Cited by 225 · see citing works
Cellular architecture of human brain metastases
Velozo, H. G., Mei, W., Robles, I., Hagerling, C., Allen, B. M., Okholm, T. L. H., Nanjaraj, A., Verbeek, T. C. A. I., Kalavacherla, S., van Gogh, M., et al. (2022) · Cell · doi:10.1016/j.cell.2021.12.043 · Cited by 221 · see citing works
Metabolic Cooperation and Competition in the Tumor Microenvironment: Implications for Therapy
Gupta, S., Roy, A., & Dwarakanath, B. S. R. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00068 · Cited by 218 · see citing works
Metabolic Barriers to T Cell Function in Tumors
Sugiura, A., & Rathmell, J. C. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1701041 · Cited by 208 · see citing works
β-Adrenergic signaling blocks murine CD8+ T-cell metabolic reprogramming during activation: a mechanism for immunosuppression by adrenergic stress
Qiao, G., Bucsek, M. J., Winder, N. M., Chen, M., Giridharan, T., Olejniczak, S. H., Hylander, B. L., & Repasky, E. A. (2018) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-018-2243-8 · Cited by 209 · see citing works
A genome-scale gain-of-function CRISPR screen in CD8 T cells identifies proline metabolism as a means to enhance CAR-T therapy
Ye, L., Park, J. J.-Y., Peng, L., Yang, Q., Chow, R. D.-W., Dong, M. B., Lam, S. Z., Guo, J., Tang, E., Zhang, Y., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.02.009 · Cited by 204 · see citing works
Immunometabolism in the Single-Cell Era
Artyomov, M. N., & den Bossche, J. V. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.09.013 · Cited by 201 · see citing works
Hypoxia induces HIF1α-dependent epigenetic vulnerability in triple negative breast cancer to confer immune effector dysfunction and resistance to anti-PD-1 immunotherapy
Ma, S., Zhao, Y., Lee, W. C., Ong, L.-T., Lee, P. L., Jiang, Z., Oguz, G., Niu, Z., Liu, M., Goh, J. Y., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-31764-9 · Cited by 200 · see citing works
Role of mitochondrial alterations in human cancer progression and cancer immunity
Wang, S., Tseng, L., & Lee, H. (2023) · Journal of Biomedical Science · doi:10.1186/s12929-023-00956-w · Cited by 208 · see citing works
Chronic lymphocytic leukemia cells impair mitochondrial fitness in CD8+ T cells and impede CAR T-cell efficacy
van Bruggen, J. A. C., Martens, A. W. J., Fraietta, J. A., Hofland, T., Tonino, S. H., Eldering, E., Levin, M.-D., Siska, P. J., Endstra, S., Rathmell, J. C., et al. (2019) · Blood · doi:10.1182/blood.2018885863 · Cited by 187 · see citing works
Microvesicles transfer mitochondria and increase mitochondrial function in brain endothelial cells
D’souza, A. A., Burch, A. M., Dave, K. M., Sreeram, A., Reynolds, M. J., Dobbins, D. X., Kamte, Y. S., Zhao, W., Sabatelle, C., Joy, G. M., et al. (2021) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.08.038 · Cited by 192 · see citing works
mTOR signaling at the crossroads of environmental signals and T‐cell fate decisions
Huang, H., Long, L., Zhou, P., Chapman, N. M., & Chi, H. (2020) · Immunological Reviews · doi:10.1111/imr.12845 · Cited by 193 · see citing works
Transforming growth factor-β-regulated mTOR activity preserves cellular metabolism to maintain long-term T cell responses in chronic infection
Gabriel, S. S., Tsui, C., Chisanga, D., Weber, F., Llano-León, M., Gubser, P. M., Bartholin, L., Souza-Fonseca-Guimarães, F., Huntington, N. D., Shi, W., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.06.007 · Cited by 193 · see citing works
Pharmacologic Screening Identifies Metabolic Vulnerabilities of CD8+ T Cells
Drijvers, J. M., Gillis, J. E., Muijlwijk, T., Nguyen, T. H., Gaudiano, E. F., Harris, I. S., LaFleur, M. W., Ringel, A. E., Yao, C.-H., Kurmi, K., et al. (2020) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-20-0384 · Cited by 190 · see citing works
Metabolic Modulation of Immunity: A New Concept in Cancer Immunotherapy
Guerra, L., Bonetti, L., & Brenner, D. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107848 · Cited by 186 · see citing works
Dysfunction of exhausted T cells is enforced by MCT11-mediated lactate metabolism
Peralta, R. M., Xie, B., Lontos, K., Nieves-Rosado, H. M., Spahr, K., Joshi, S. K., Ford, B. R., Quann, K., Frisch, A. T., Dean, V. G., et al. (2024) · Nature Immunology · doi:10.1038/s41590-024-01999-3 · Cited by 190 · see citing works
Self-citation
Involvement of tumor immune microenvironment metabolic reprogramming in colorectal cancer progression, immune escape, and response to immunotherapy
Nicolini, A., & Ferrari, P. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1353787 · Cited by 187 · see citing works
Macrophage-derived CCL22 promotes an immunosuppressive tumor microenvironment via IL-8 in malignant pleural effusion
Wang, D., Yang, L., Yue, D., Cao, L., Li, L., Wang, D., Ping, Y., Shen, Z., Zheng, Y., Wang, L., et al. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.03.040 · Cited by 183 · see citing works
Current issues and perspectives in PD-1 blockade cancer immunotherapy
Chamoto, K., Hatae, R., & Honjo, T. (2020) · International Journal of Clinical Oncology · doi:10.1007/s10147-019-01588-7 · Cited by 180 · see citing works
Combination of metabolic intervention and T cell therapy enhances solid tumor immunotherapy
Hao, M., Hou, S., Li, W., Li, K., Xue, L., Hu, Q., Zhu, L., Chen, Y., Sun, H., Ju, C., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aaz6667 · Cited by 183 · see citing works
Mitochondrial quality control in human health and disease
Liu, B., Xu, C.-Z., Liu, Y., Lu, Z., Fu, T.-L., Li, G., Deng, Y., Luo, G., Ding, S. Z., Li, N., et al. (2024) · Military Medical Research · doi:10.1186/s40779-024-00536-5 · Cited by 189 · see citing works
Chronic Adrenergic Stress Contributes to Metabolic Dysfunction and an Exhausted Phenotype in T Cells in the Tumor Microenvironment
Qiao, G., Chen, M., Mohammadpour, H., MacDonald, C. R., Bucsek, M. J., Hylander, B. L., Barbi, J. J., & Repasky, E. A. (2021) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-20-0445 · Cited by 179 · see citing works
Counteracting CAR T cell dysfunction
Poorebrahim, M., Melief, J., de Coaña, Y. P., Wickström, S. L., Cid-Arregui, Á., & Kiessling, R. W. (2020) · Oncogene · doi:10.1038/s41388-020-01501-x · Cited by 169 · see citing works
CAR-T cell combination therapy: the next revolution in cancer treatment
Al-Haideri, M. T., Tondok, S. B., Safa, S. H., Maleki, A. H., Rostami, S. M., Jalil, A. T., Al-Gazally, M. E., Alsaikhan, F., Rizaev, J. A., Mohammad, T. A. M., et al. (2022) · Cancer Cell International · doi:10.1186/s12935-022-02778-6 · Cited by 167 · see citing works
Mitochondrial activity in T cells
Desdín-Micó, G., Soto‐Heredero, G., & Mittelbrunn, M. (2017) · Mitochondrion · doi:10.1016/j.mito.2017.10.006 · Cited by 162 · see citing works
Impact of sarcopenia in patients with advanced non–small cell lung cancer treated with PD-1 inhibitors: A preliminary retrospective study
Shiroyama, T., Nagatomo, I., Koyama, S., Hirata, H., Nishida, S., Miyake, K., Fukushima, K., Shirai, Y., Mitsui, Y., Takata, S., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-39120-6 · Cited by 162 · see citing works
Dysfunctional T cell metabolism in the tumor microenvironment
Beckermann, K. E., Dudzinski, S. O., & Rathmell, J. C. (2017) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2017.04.003 · Cited by 159 · see citing works
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 157 · see citing works
Impaired enolase 1 glycolytic activity restrains effector functions of tumor-infiltrating CD8 + T cells
Gemta, L. F., Siska, P. J., Nelson, M. E., Gao, X., Liu, X., Locasale, J. W., Yagita∥, H., Slingluff, C. L., Hoehn, K. L., Rathmell, J. C., et al. (2019) · Science Immunology · doi:10.1126/sciimmunol.aap9520 · Cited by 155 · see citing works
Reactive Oxygen Species and Antitumor Immunity—From Surveillance to Evasion
Kotsafti, A., Scarpa, M., Castagliuolo, I., & Scarpa, M. (2020) · Cancers · doi:10.3390/cancers12071748 · Cited by 157 · see citing works
Expansion of T memory stem cells with superior anti-tumor immunity by Urolithin A-induced mitophagy
Denk, D., Petrocelli, V., Conche, C., Drachsler, M. W., Ziegler, P. K., Braun, A., Kress, A., Nicolas, A. M., Mohs, K., Becker, C., et al. (2022) · Immunity · doi:10.1016/j.immuni.2022.09.014 · Cited by 153 · see citing works
Regulatory T cell-mediated immunosuppression orchestrated by cancer: towards an immuno-genomic paradigm for precision medicine
Kumagai, S., Itahashi, K., & Nishikawa, H. (2024) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-024-00870-6 · Cited by 163 · see citing works
Mitochondrial Metabolism Regulation of T Cell–Mediated Immunity
Steinert, E. M., Vasan, K., & Chandel, N. S. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101819-082015 · Cited by 153 · see citing works

Abstract IA08: Identifying and overcoming metabolic checkpoints to antitumor immunity
Delgoffe, G. M. (2016) · Cancer Immunology Research · doi:10.1158/2326-6066.imm2016-ia08
Self-citation
Dysfunctional T cell metabolism in the tumor microenvironment
Beckermann, K. E., Dudzinski, S. O., & Rathmell, J. C. (2017) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2017.04.003 · Cited by 159 · see citing works
Immunometabolic requirements of T cell activation and exhaustion
Scharping, N. E. (2019) · D-Scholarship@Pitt (University of Pittsburgh)
Self-citation
Metabolic Barriers to T Cell Function in Tumors
Sugiura, A., & Rathmell, J. C. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1701041 · Cited by 208 · see citing works
Abstract 632: The metabolic requirements for effective immunotherapy
Scharping, N. E., Menk, A. V., & Delgoffe, G. M. (2018) · Cancer Research · doi:10.1158/1538-7445.am2018-632
Self-citation

Authors: Scharping, N. E., Menk, A. V., Moreci, R. S., Whetstone, R. D., Dadey, R. E., Watkins, S. C., Ferris, R. L., & Delgoffe, G. M.
Affiliations: University of Pittsburgh (US)
UPMC Hillman Cancer Center (US)
Corresponding author: Delgoffe, Greg M.
ORCID: Scharping, Nicole E.
Menk, Ashley V.
Dadey, Rebekah E.
Watkins, Simon C.
Ferris, Robert L.
Delgoffe, Greg M.
Venue: Immunity
Publisher: Elsevier BV
Published: 2016-08
Volume: 45
Issue: 2
Pages: 374-388
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2016.07.009
PMC: PMC5207350
OpenAlex: W4294138012
Cited by: 848
References: 44
Citations by year: 2026: 136 · 2025: 111 · 2024: 113 · 2023: 97 · 2022: 109 · 2021: 90 · 2020: 76 · 2019: 42 · 2018: 33 · 2017: 34 · 2016: 7
FWCI: 20.82
Type: journal article
Language: en
Update notices: erratum (2016-09-20)
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 380 d)
Locations: Immunity (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (1s10od016236-01)
National Cancer Institute (P50CA121973, P50CA097190, P30CA047904)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Keywords: tumor microenvironment, PGC-1α, Akt signaling, T cell metabolism, oxidative metabolism, tumor-infiltrating T cells, T cell dysfunction, immunosuppression, metabolic reprogramming, cancer immunotherapy
MeSH terms: Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Colonic Neoplasms, Humans, Mice, Inbred C57BL, Mice, Transgenic, Mitochondria, Neoplasms, Experimental, T-Lymphocytes, Signal Transduction, Lymphocytes, Tumor-Infiltrating, Oxidative Stress, Cell Line, Tumor, PPAR gamma, Oncogene Protein v-akt, Mice, Tumor Microenvironment, Cellular Reprogramming

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

The Tumor Microenvironment Represses T Cell Mitochondrial Biogenesis to Drive Intratumoral T Cell Metabolic Insufficiency and Dysfunction

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks