Mitochondrial stress induced by continuous stimulation under hypoxia rapidly drives T cell exhaustion
Open accessAbstract
Cancer and chronic infections induce T cell exhaustion, a hypofunctional fate carrying distinct epigenetic, transcriptomic and metabolic characteristics. However, drivers of exhaustion remain poorly understood. As intratumoral exhausted T cells experience severe hypoxia, we hypothesized that metabolic stress alters their responses to other signals, specifically, persistent antigenic stimulation. In vitro, although CD8+ T cells experiencing continuous stimulation or hypoxia alone differentiated into functional effectors, the combination rapidly drove T cell dysfunction consistent with exhaustion. Continuous stimulation promoted Blimp-1-mediated repression of PGC-1α-dependent mitochondrial reprogramming, rendering cells poorly responsive to hypoxia. Loss of mitochondrial function generated intolerable levels of reactive oxygen species (ROS), sufficient to promote exhausted-like states, in part through phosphatase inhibition and the consequent activity of nuclear factor of activated T cells. Reducing T cell-intrinsic ROS and lowering tumor hypoxia limited T cell exhaustion, synergizing with immunotherapy. Thus, immunologic and metabolic signaling are intrinsically linked: through mitigation of metabolic stress, T cell differentiation can be altered to promote more functional cellular fates.
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
Cites
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?
Both oxidative and ER stress have been shown to contribute to T cell dysfunction across different tumor types.
“Even though both oxidative and ER stress have been shown to contribute to T cell dysfunction across different tumor types (44-51),”
From Bile acid synthesis impedes tumor-specific T cell responses during liver cancer (2025) · cites this paper as [48]
The Results (‘Mitigating ROS or hypoxia alleviates T cell exhaustion’; page unavailable) report that reducing T-cell ROS protected against tumor-induced exhaustion, supporting the oxidative-stress part. Our copy does not show that ER stress contributes to T-cell dysfunction, or establish the claim across different tumor types; the tumor experiment described here used B16 melanoma. (LLM, conf=0.87)
Experimental — accuracy not yet measuredConsiderable evidence in mouse models has shown that hypoxia promotes tumor escape from immune surveillance and immunotherapy.
“Considerable evidence in mouse models has shown that hypoxia promotes tumor escape from immune surveillance and immunotherapy13–19.”
There are opposite reports showing that tumor hypoxia induces mouse T cell exhaustion and resistance to immunotherapy and depletion of HIF1α increases NK cell activity and tumor infiltration.
“there are also opposite reports showing that tumor hypoxia induces mouse T cell exhaustion and resistance to immunotherapy and depletion of HIF1α increases NK cell activity and tumor infiltration16,17,19,48,49.”
Hypoxia and continued antigen stimulation can induce mitochondrial stress in mouse T cells, leading to terminal exhaustion but in a HIF1α-independent manner.
“a recent study showed that hypoxia and continued antigen stimulation could induce mitochondrial stress in mouse T cells, leading to terminal exhaustion but in a HIF1α-independent manner19.”
Current studies have focused on the role of hypoxia-induced metabolic reprogramming in causing T cell dysfunction and exhaustion.
“Current studies have focused on the role of hypoxia-induced metabolic reprogramming in causing T cell dysfunction and exhaustion16,19,52–55.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
ROS function in redox signaling and oxidative stress
Schieber, M., & Chandel, N. S. (2014) · Current Biology · doi:10.1016/j.cub.2014.03.034 · Cited by 6,931 · 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
Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma
Motzer, R. J., Penkov, K., Haanen, J. B. A. G., Rini, B. I., Albiges, L. K., Campbell, M. T., Venugopal, B., Kollmannsberger, C., Négrier, S., Uemura, M., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1816047 · Cited by 2,512 · see citing works
St-Pierre, J., Drori, S., Uldry, M., Silvaggi, J. M., Rhee, J., Jäger, S., Handschin, C., Zheng, K., Lin, J., Yang, W., et al. (2006) · Cell · doi:10.1016/j.cell.2006.09.024 · Cited by 2,233 · see citing works
Miller, B. C., Sen, D. R., Al Abosy, R., Bi, K., Virkud, Y. V., LaFleur, M. W., Yates, K. B., Lako, A., Felt, K., Naik, G. S., et al. (2019) · Nature Immunology · doi:10.1038/s41590-019-0312-6 · Cited by 2,087 · see citing works
Defining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma
Sade-Feldman, M., Yizhak, K., Bjorgaard, S. L., Ray, J. P., de Boer, C. G., Jenkins, R. W., Lieb, D. J., Chen, J. H., Frederick, D. T., Barzily-Rokni, M., et al. (2018) · Cell · doi:10.1016/j.cell.2018.10.038 · Cited by 2,053 · see citing works
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
Mitochondrial reactive oxygen species trigger hypoxia-induced transcription
Chandel, N. S., Maltepe, E., Goldwasser, E., Mathieu, C. E., Simon, M. C., & Schumacker, P. T. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.20.11715 · Cited by 1,926 · see citing works
Blank, C. U., Haining, W. N., Held, W., Hogan, P. G., Kallies, A., Lugli, E., Lynn, R. C., Philip, M., Rao, A., Restifo, N. P., et al. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0221-9 · Cited by 1,603 · see citing works
Cancer metabolism: a therapeutic perspective
Martinez-Outschoorn, U. E., Peiris-Pagés, M., Pestell, R. G., Sotgia, F., & Lisanti, M. P. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.60 · Cited by 1,505 · 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
Li, N., Ragheb, K., Lawler, G., Sturgis, J., Rajwa, B. P., Melendez, J. A., & Robinson, J. P. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210432200 · Cited by 1,434 · see citing works
Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade
Pauken, K. E., Sammons, M. A., Odorizzi, P. M., Manne, S., Godec, J., Khan, O., Drake, A. M., Chen, Z., Sen, D. R., Kurachi, M., et al. (2016) · Science · doi:10.1126/science.aaf2807 · Cited by 1,348 · see citing works
Sena, L. A., Li, S., Jairaman, A., Prakriya, M., Ezponda, T., Hildeman, D. A., Wang, C.-R., Schumacker, P. T., Licht, J. D., Perlman, H., et al. (2013) · Immunity · doi:10.1016/j.immuni.2012.10.020 · Cited by 1,338 · 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
Self-citationVEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors
Voron, T., Colussi, O., Marcheteau, E., Pernot, S., Nizard, M., Pointet, A.-L., Latreche, S., Bergaya, S., Benhamouda, N., Tanchot, C., et al. (2015) · Journal of Experimental Medicine · doi:10.1084/jem.20140559 · Cited by 1,179 · see citing works
Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion
Leone, R. D., Zhao, L., Englert, J. M., Sun, I.-M., Oh, M.-H., Sun, I.-H., Arwood, M. L., Bettencourt, I. A., Patel, C. H., Wen, J., et al. (2019) · Science · doi:10.1126/science.aav2588 · Cited by 1,169 · cited 1× · see citing works
“We and others have also shown correcting this faulty metabolic state (through a variety of approaches) can invigorate immunity and enable immunotherapeutic outcomes 16–20 .”
TNF and ROS crosstalk in inflammation
Blaser, H., Dostert, C., Mak, T. W., & Brenner, D. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.12.002 · Cited by 1,008 · see citing works
The epigenetic landscape of T cell exhaustion
Sen, D. R., Kaminski, J., Barnitz, R. A., Kurachi, M., Gerdemann, U., Yates, K. B., Tsao, H.-W., Godec, J., LaFleur, M. W., Brown, F. D., et al. (2016) · Science · doi:10.1126/science.aae0491 · Cited by 986 · see citing works
Chromatin states define tumour-specific T cell dysfunction and reprogramming
Philip, M., Fairchild, L., Sun, L., Horste, E. L., Camara, S., Shakiba, M., Scott, A. C., Viale, A., Lauer, P., Merghoub, T., et al. (2017) · Nature · doi:10.1038/nature22367 · Cited by 933 · see citing works
Progenitor and Terminal Subsets of CD8 + T Cells Cooperate to Contain Chronic Viral Infection
Paley, M., Kroy, D. C., Odorizzi, P. M., Johnnidis, J. B., Dolfi, D. V., Barnett, B. E., Bikoff, E. K., Robertson, E. J., Lauer, G. M., Reiner, S. L., et al. (2012) · Science · doi:10.1126/science.1229620 · Cited by 903 · see citing works
Bengsch, B., Johnson, A. L., Kurachi, M., Odorizzi, P. M., Pauken, K. E., Attanasio, J., Stelekati, E., McLane, L. M., Paley, M. A., Delgoffe, G. M., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.07.008 · Cited by 868 · see citing works
Self-citationThe Transcription Factor NFAT Promotes Exhaustion of Activated CD8 + T Cells
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., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.01.006 · Cited by 857 · see citing works
Scharping, N. E., Menk, A. V., Moreci, R. S., Whetstone, R. D., Dadey, R. E., Watkins, S. C., Ferris, R. L., & Delgoffe, G. M. (2016) · Immunity · doi:10.1016/j.immuni.2016.07.009 · Cited by 848 · see citing works
Self-citationScharping, N. E., Menk, A. V., Moreci, R. S., Whetstone, R. D., Dadey, R., Watkins, S. C., Ferris, R. L., & Delgoffe, G. M. (2016) · Immunity · doi:10.1016/j.immuni.2016.08.009 · Cited by 705 · see citing works
Self-citationHypoxia-inducible factors enhance the effector responses of CD8(+) T cells to persistent antigen
Doedens, A. L., Phan, A. T., Stradner, M. H., Fujimoto, J. K., Nguyen, J. V., Yang, E., Johnson, R. S., & Goldrath, A. W. (2013) · Nature Immunology · doi:10.1038/ni.2714 · Cited by 660 · see citing works
Defining the role of the tumor vasculature in antitumor immunity and immunotherapy
Schaaf, M. B., Garg, A. D., & Agostinis, P. (2018) · Cell Death & Disease · doi:10.1038/s41419-017-0061-0 · Cited by 629 · see citing works
Molecular regulation of effector and memory T cell differentiation
Chang, J. T., Wherry, E. J., & Goldrath, A. W. (2014) · Nature Immunology · doi:10.1038/ni.3031 · Cited by 578 · see citing works
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
Adaptive plasticity of IL-10+ and IL-35+ Treg cells cooperatively promotes tumor T cell exhaustion
Sawant, D. V., Yano, H., Chikina, M. D., Zhang, Q., Liao, M., Liu, C., Callahan, D. J., Sun, Z., Sun, T., Tabib, T., et al. (2019) · Nature Immunology · doi:10.1038/s41590-019-0346-9 · Cited by 547 · see citing works
Self-citationAn HIF-1α/VEGF-A Axis in Cytotoxic T Cells Regulates Tumor Progression
Palazon, A., Tyrakis, P. A., Macias, D., Veliça, P., Rundqvist, H., Fitzpatrick, S., Vojnovic, N., Phan, A. T., Loman, N., Hedenfalk, I., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.10.003 · Cited by 521 · 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-citationMolecular and Transcriptional Basis of CD4+ T Cell Dysfunction during Chronic Infection
Crawford, A., Angelosanto, J., Kao, C., Doering, T. A., Odorizzi, P. M., Barnett, B. E., & Wherry, E. J. (2014) · Immunity · doi:10.1016/j.immuni.2014.01.005 · Cited by 495 · see citing works
Cellular Metabolic Stress: Considering How Cells Respond to Nutrient Excess
Wellen, K. E., & Thompson, C. B. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.10.004 · Cited by 486 · see citing works
Shin, H., Blackburn, S. D., Intlekofer, A. M., Kao, C., Angelosanto, J., Reiner, S. L., & Wherry, E. J. (2009) · Immunity · doi:10.1016/j.immuni.2009.06.019 · Cited by 481 · see citing works
Induction and transcriptional regulation of the co-inhibitory gene module in T cells
Chihara, N., Madi, A., Kondo, T., Zhang, H., Acharya, N., Singer, M., Nyman, J., Marjanovic, N. D., Kowalczyk, M. S., Wang, C., et al. (2018) · Nature · doi:10.1038/s41586-018-0206-z · 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
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
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
The mechanism of mitochondrial superoxide production by the cytochrome bc1 complex
Dröse, S., & Brandt, U. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803236200 · Cited by 386 · see citing works
Mitochondrial Respiration Controls Lysosomal Function during Inflammatory T Cell Responses
Baixauli, F., Acín‐Pérez, R., Villarroya‐Beltri, C., Mazzeo, C., Núñez‐Andrade, N., Gabandé‐Rodríguez, E., Ledesma, M. D., Blázquez, A., Martín, M. A., Falcón‐Pérez, J. M., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.07.020 · Cited by 327 · see citing works
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-citationTumor 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-citationCD4 Helper and CD8 Cytotoxic T Cell Differentiation
Taniuchi, I. (2018) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042617-053411 · Cited by 228 · see citing works
Consequences of Hyperoxia and the Toxicity of Oxygen in the Lung
Mach, W. J., Thimmesch, A. R., Pierce, J. T., & Pierce, J. D. (2011) · Nursing Research and Practice · doi:10.1155/2011/260482 · Cited by 215 · see citing works
Phan, A. T., Doedens, A. L., Palazón, A., Tyrakis, P. A., Cheung, K. P., Johnson, R. S., & Goldrath, A. W. (2016) · Immunity · doi:10.1016/j.immuni.2016.10.017 · Cited by 201 · see citing works
Li, Y., Patel, S. P., Roszik, J., & Qin, Y. W. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01591 · Cited by 195 · see citing works
Horton, B. L., Williams, J. B., Cabanov, A., Spranger, S., & Gajewski, T. F. (2017) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-17-0249 · Cited by 167 · see citing works
Gropper, Y., Feferman, T., Shalit, T., Salame, T., Porat, Z., & Shakhar, G. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.08.071 · Cited by 166 · see citing works
Neuropilin-1 is a T cell memory checkpoint limiting long-term antitumor immunity
Liu, C., Somasundaram, A., Manne, S., Gocher, A. M., Szymczak-Workman, A. L., Vignali, K. M., Scott, E. N., Normolle, D. P., John Wherry, E., Lipson, E. J., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0733-2 · Cited by 151 · see citing works
Bacik, I., Cox, J. H., Anderson, R., et al. (1994) · The Journal of Immunology · doi:10.4049/jimmunol.152.2.381 · Cited by 145 · see citing works
Chinopoulos, C. (2013) · Journal of Neuroscience Research · doi:10.1002/jnr.23196 · Cited by 142 · see citing works
Tumor Microenvironment Metabolism: A New Checkpoint for Anti-Tumor Immunity
Scharping, N. E., & Delgoffe, G. M. (2016) · Vaccines · doi:10.3390/vaccines4040046 · Cited by 119 · see citing works
Self-citationEndoplasmic Reticulum Stress Contributes to Mitochondrial Exhaustion of CD8+ T Cells
Hurst, K. E., Lawrence, K. A., Essman, M. T., Walton, Z. J., Leddy, L. R., & Thaxton, J. E. (2019) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-18-0182 · Cited by 102 · see citing works
Tick-TOX, it’s time for T cell exhaustion
Mann, T. H., & Kaech, S. M. (2019) · Nature Immunology · doi:10.1038/s41590-019-0478-y · Cited by 69 · see citing works
Poholek, A. C., Jankovic, D. L., Villarino, A. V., Petermann, F., Hettinga, A., Shouval, D. S., Snapper, S. B., Kaech, S. M., Brooks, S. R., Vahedi, G., et al. (2016) · Science Immunology · doi:10.1126/sciimmunol.aaf8612 · Cited by 34 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions
Chen, Z., Han, F., Du, Y., Shi, H., & Zhou, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01332-8 · Cited by 1,612 · see citing works
Mittelbrunn, M., & Kroemer, G. (2021) · Nature Immunology · doi:10.1038/s41590-021-00927-z · Cited by 702 · see citing works
Baessler, A., & Vignali, D. A. A. (2024) · Annual Review of Immunology · doi:10.1146/annurev-immunol-090222-110914 · Cited by 420 · see citing works
Tumour burden and efficacy of immune-checkpoint inhibitors
Dall’Olio, F. G., Marabelle, A., Caramella, C., Garcia, C., Aldea, M., Chaput, N., Robert, C., & Besse, B. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00564-3 · Cited by 350 · see citing works
Hypoxia drives CD39-dependent suppressor function in exhausted T cells to limit antitumor immunity
Vignali, P. D. A., DePeaux, K., Watson, M. J., Ye, C., Ford, B. R., Lontos, K., McGaa, N. K., Scharping, N. E., Menk, A. V., Robson, S. C., et al. (2023) · Nature Immunology · doi:10.1038/s41590-022-01379-9 · Cited by 269 · see citing works
Self-citationMa, 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
Bile acid synthesis impedes tumor-specific T cell responses during liver cancer
Varanasi, S. K., Chen, D., Liu, Y., Johnson, M. A., Miller, C. M., Ganguly, S., Lande, K., LaPorta, M. A., Hoffmann, F. A., Mann, T. H., et al. (2025) · Science · doi:10.1126/science.adl4100 · Cited by 177 · see citing works
Carbon source availability drives nutrient utilization in CD8+ T cells
Kaymak, I., Luda, K. M., Duimstra, L. R., Ma, E. H., Longo, J., Dahabieh, M. S., Faubert, B., Oswald, B. M., Watson, M. J., Kitchen-Goosen, S. M., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.07.012 · Cited by 160 · see citing works
Autoreactive CD8+ T cells are restrained by an exhaustion-like program that is maintained by LAG3
Grebinoski, S., Zhang, Q., Cillo, A. R., Manne, S., Xiao, H., Brunazzi, E. A., Tabib, T., Cardello, C., Lian, C. G., Murphy, G. F., et al. (2022) · Nature Immunology · doi:10.1038/s41590-022-01210-5 · Cited by 107 · see citing works
NUDT1 promotes the accumulation and longevity of CD103+ TRM cells in primary biliary cholangitis
Huang, B., Lyu, Z., Qian, Q., Chen, Y., Zhang, J., Li, B., Li, Y., Liang, J., Liu, Q., Li, Y., et al. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.06.014 · Cited by 60 · see citing works
Akhtar, A., Shakir, M., Ansari, M. S., Divya, Faizan, M. I., Chauhan, V., Singh, A., Alam, R., Azmi, I., Sharma, S., et al. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102021 · Cited by 21 · see citing works
The potential role of CMC1 as an immunometabolic checkpoint in T cell immunity
Chen, Y., Gao, J., Ma, M., Wang, K., Liu, F., Yang, F., Zou, X., Cheng, Z., & Wu, D. (2024) · OncoImmunology · doi:10.1080/2162402x.2024.2344905 · Cited by 13 · see citing works
- Authors
- 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., Poholek, A. C., & Delgoffe, G. M.
- Affiliations
- University of Pittsburgh (US)
- Tsinghua University (CN)
- Corresponding author
- Delgoffe, Greg M.
- ORCID
- Venue
- Nature Immunology
- Published
- 2021-01-04
- Volume
- 22
- Issue
- 2
- Pages
- 205-215
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC7971090
- OpenAlex
- W3119279345
- Cited by
- 897
- References
- 57
- Citations by year
- 2026: 198 · 2025: 202 · 2024: 165 · 2023: 147 · 2022: 122 · 2021: 63
- FWCI
- 46.83
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (F99CA222711, F31CA247129, P50CA121973, F30CA247034, K00CA222711, T32CA082084, P50CA097190, P30CA047904)
- National Institute of Allergy and Infectious Diseases (DP2AI136598, R21AI135367, T32AI089443)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- T cell exhaustion, mitochondrial stress, hypoxia, Blimp-1, PGC-1α, mitochondrial reprogramming, reactive oxygen species, NFAT, CD8+ T cells, tumor immunology, immunotherapy, metabolic stress
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Tumor Hypoxia, Positive Regulatory Domain I-Binding Factor 1, Animals, Energy Metabolism, Female, Humans, Lymphocyte Activation, Male, Melanoma, Experimental, Mice, Inbred C57BL, Mice, Transgenic, Mitochondria, Signal Transduction, Lymphocytes, Tumor-Infiltrating, Reactive Oxygen Species, CD8-Positive T-Lymphocytes, Coculture Techniques, Cell Line, Tumor, Mice, HEK293 Cells, Tumor Microenvironment
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
