The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy
Open accessAbstract
Chronic viral infections are characterized by a state of CD8+ T-cell dysfunction that is associated with expression of the programmed cell death 1 (PD-1) inhibitory receptor. A better understanding of the mechanisms that regulate CD8+ T-cell responses during chronic infection is required to improve immunotherapies that restore function in exhausted CD8+ T cells. Here we identify a population of virus-specific CD8+ T cells that proliferate after blockade of the PD-1 inhibitory pathway in mice chronically infected with lymphocytic choriomeningitis virus (LCMV). These LCMV-specific CD8+ T cells expressed the PD-1 inhibitory receptor, but also expressed several costimulatory molecules such as ICOS and CD28. This CD8+ T-cell subset was characterized by a unique gene signature that was related to that of CD4+ T follicular helper (T FH) cells, CD8+ T cell memory precursors and haematopoietic stem cell progenitors, but that was distinct from that of CD4+ T H 1 cells and CD8+ terminal effectors. This CD8+ T-cell population was found only in lymphoid tissues and resided predominantly in the T-cell zones along with naive CD8+ T cells. These PD-1+CD8+ T cells resembled stem cells during chronic LCMV infection, undergoing self-renewal and also differentiating into the terminally exhausted CD8+ T cells that were present in both lymphoid and non-lymphoid tissues. The proliferative burst after PD-1 blockade came almost exclusively from this CD8+ T-cell subset. Notably, the transcription factor TCF1 had a cell-intrinsic and essential role in the generation of this CD8+ T-cell subset. These findings provide a better understanding of T-cell exhaustion and have implications in the optimization of PD-1-directed immunotherapy in chronic infections and cancer.
Overview
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
Verification
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Progenitor Tex (Tprog) cells retain stemness and self-renewal capacity that respond to immune checkpoint blockade (ICB) therapies and differentiate into intermediate T (Tint) cells with cytolytic capacity8–10.”
From Proteotoxic stress response drives T cell exhaustion and immune evasion (2025) · cites this paper as [10]
Experimental — accuracy not yet measuredIn the citing paper
“Two recent studies have shown that it is indeed CD28-expressing cells rather than already terminally differentiated effector cells that respond to PD-1 blockade with a proliferative burst and differentiation (94, 95).”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [94]
In the citing paper
“Preclinical models demonstrated that PD-1 blockade results in tumor rejection through reinvigoration of exhausted CD8 T cells that express PD-1, LAG3, and TIM3 and expansion of CD8 T cells, a hallmark of response to anti-PD-1 therapy (16).”
From The Next Decade of Immune Checkpoint Therapy (2021) · cites this paper as [16]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Takeda, K., Kaisho, T., & Akira, S. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.141126 · Cited by 6,143
The future of immune checkpoint therapy
Sharma, P., & Allison, J. P. (2015) · Science · doi:10.1126/science.aaa8172 · Cited by 4,878
Restoring function in exhausted CD8 T cells during chronic viral infection
Barber, D. L., Wherry, E. J., Masopust, D., Zhu, B., Allison, J. P., Sharpe, A. H., Freeman, G. J., & Ahmed, R. (2005) · Nature · doi:10.1038/nature04444 · Cited by 4,057
Self-citationFollicular Helper CD4 T Cells (T FH )
Crotty, S. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101400 · Cited by 2,738
A role for Wnt signalling in self-renewal of haematopoietic stem cells
Reya, T., Duncan, A. W., Ailles, L., Domen, J., Scherer, D. C., Willert, K., Hintz, L., Nusse, R., & Weissman, I. L. (2003) · Nature · doi:10.1038/nature01593 · Cited by 2,159
Blackburn, S. D., Shin, H., Haining, W. N., Zou, T., Workman, C. J., Polley, A., Betts, M. R., Freeman, G. J., Vignali, D. A. A., & Wherry, E. J. (2009) · Nature Immunology · doi:10.1038/ni.1679 · Cited by 2,062
Self-citationViral Immune Evasion Due to Persistence of Activated T Cells Without Effector Function
Zajac, A. J., Blattman, J. N., Murali-Krishna, K., Sourdive, D. J. D., Suresh, M., Altman, J. D., & Ahmed, R. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.12.2205 · Cited by 1,978
Self-citationCounting Antigen-Specific CD8 T Cells: A Reevaluation of Bystander Activation during Viral Infection
Murali‐Krishna, K., Altman, J. D., Suresh, M., Sourdive, D. J. D., Zajac, A. J., Miller, J. D., Slansky, J. E., & Ahmed, R. (1998) · Immunity · doi:10.1016/s1074-7613(00)80470-7 · Cited by 1,918
Self-citationJoshi, N. S., Cui, W., Chandele, A., Lee, H. K., Urso, D. R., Hagman, J., Gapin, L., & Kaech, S. M. (2007) · Immunity · doi:10.1016/j.immuni.2007.07.010 · Cited by 1,861
Monney, L., Sabatos, C. A., Gaglia, J. L., Ryu, A., Waldner, H., Chernova, T., Manning, S., Greenfield, E. A., Coyle, A. J., Sobel, R. A., et al. (2002) · Nature · doi:10.1038/415536a · Cited by 1,677
Self-citation
Cited by
Sorted by citations
Elements of cancer immunity and the cancer–immune set point
Chen, D. S., & Mellman, I. (2017) · Nature · doi:10.1038/nature21349 · Cited by 5,352
Fundamental Mechanisms of Immune Checkpoint Blockade Therapy
Wei, S. C., Duffy, C. R., & Allison, J. P. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0367 · Cited by 3,088
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
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
Self-citationCD8 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 2,054
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 2,054
Self-citationSiddiqui, I., Schaeuble, K., Chennupati, V., Fuertes Marraco, S. A., Calderon-Copete, S., Pais Ferreira, D., Carmona, S. J., Scarpellino, L., Gfeller, D., Pradervand, S., et al. (2019) · Immunity · doi:10.1016/j.immuni.2018.12.021 · Cited by 1,679
T cell costimulatory receptor CD28 is a primary target for PD-1–mediated inhibition
Hui, E., Cheung, J., Zhu, J., Su, X., Taylor, M. J., Wallweber, H. A., Sasmal, D. K., Huang, J., Kim, J. M., Mellman, I., et al. (2017) · Science · doi:10.1126/science.aaf1292 · Cited by 1,689
T-cell invigoration to tumour burden ratio associated with anti-PD-1 response
Huang, A. C., Postow, M. A., Orlowski, R. J., Mick, R., Bengsch, B., Manne, S., Xu, W., Harmon, S., Giles, J. R., Wenz, B., et al. (2017) · Nature · doi:10.1038/nature22079 · Cited by 1,664
Clonal replacement of tumor-specific T cells following PD-1 blockade
Yost, K. E., Satpathy, A. T., Wells, D. K., Qi, Y., Wang, C., Kageyama, R., McNamara, K. L., Granja, J. M., Sarin, K. Y., Brown, R. A., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0522-3 · Cited by 1,534
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
Self-citationT follicular helper cell biology: a decade of discovery and diseases
Crotty, S. (2019) · Immunity · doi:10.1016/j.immuni.2019.04.011 · Cited by 1,591
CD4+ T cell help in cancer immunology and immunotherapy
Borst, J., Ahrends, T., Bąbała, N., Melief, C. J. M., & Kastenmüller, W. (2018) · Nature Reviews Immunology · doi:10.1038/s41577-018-0044-0 · Cited by 1,585
CD8+ T cell states in human cancer: insights from single-cell analysis
van der Leun, A. M., Thommen, D. S., & Schumacher, T. N. (2020) · Nature reviews. Cancer · doi:10.1038/s41568-019-0235-4 · Cited by 1,487
Mechanisms of resistance to immune checkpoint inhibitors
Jenkins, R. W., Barbie, D. A., & Flaherty, K. T. (2018) · British Journal of Cancer · doi:10.1038/bjc.2017.434 · Cited by 1,383
Pan-cancer single-cell landscape of tumor-infiltrating T cells
Zheng, L., Qin, S., Si, W., Wang, A., Xing, B., Gao, R., Ren, X., Wang, L., Wu, X., Zhang, J., et al. (2021) · Science · doi:10.1126/science.abe6474 · Cited by 1,402
Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations
Seidel, J. A., Otsuka, A., & Kabashima, K. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00086 · Cited by 1,360
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
Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade
Wei, S. C., Levine, J. H., Cogdill, A. P., Zhao, Y., Anang, N.-A. A. S., Andrews, M. C., Sharma, P., Wang, J., Wargo, J. A., Pe’er, D., et al. (2017) · Cell · doi:10.1016/j.cell.2017.07.024 · Cited by 1,302
Thommen, D. S., & Schumacher, T. N. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.012 · Cited by 1,351
Thommen, D. S., Koelzer, V. H., Herzig, P., Roller, A., Trefny, M., Dimeloe, S., Kiialainen, A., Hanhart, J., Schill, C., Hess, C., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0057-z · Cited by 1,161
Tumor Interferon Signaling Regulates a Multigenic Resistance Program to Immune Checkpoint Blockade
Benci, J. L., Xu, B., Qiu, Y., Wu, T. J., Dada, H., Twyman-Saint Victor, C., Cucolo, L., Lee, D. S. M., Pauken, K. E., Huang, A. C., et al. (2016) · Cell · doi:10.1016/j.cell.2016.11.022 · Cited by 1,216
Li, H., van der Leun, A. M., Yofe, I., Lubling, Y., Gelbard-Solodkin, D., van Akkooi, A. C. J., van den Braber, M., Rozeman, E. A., Haanen, J. B. A. G., Blank, C. U., et al. (2019) · Cell · doi:10.1016/j.cell.2018.11.043 · Cited by 1,101
Beltra, J., Manne, S., Abdel-Hakeem, M. S., Kurachi, M., Giles, J. R., Chen, Z., Casella, V., Ngiow, S. F., Khan, O., Huang, Y., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.04.014 · Cited by 1,139
Arbour, K. C., Mezquita, L., Long, N., Rizvi, H., Auclin, E., Ni, A., Martínez-Bernal, G., Ferrara, R., Lai, W. V., Hendriks, L. E. L., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2018.79.0006 · Cited by 1,071
The Principles of Engineering Immune Cells to Treat Cancer
Lim, W. A., & June, C. H. (2017) · Cell · doi:10.1016/j.cell.2017.01.016 · Cited by 1,103
CD8+ T cell differentiation and dysfunction in cancer
Philip, M., & Schietinger, A. (2022) · Nature Reviews Immunology · doi:10.1038/s41577-021-00574-3 · Cited by 1,052
Clinical implications of T cell exhaustion for cancer immunotherapy
Chow, A., Perica, K., Klebanoff, C. A., & Wolchok, J. D. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00689-z · Cited by 1,044
Sun, L., Su, Y., Jiao, A., Wang, X., & Zhang, B. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01471-y · Cited by 1,153
Rescue of exhausted CD8 T cells by PD-1–targeted therapies is CD28-dependent
Kamphorst, A. O., Wieland, A., Nasti, T., Yang, S., Zhang, R., Barber, D. L., Konieczny, B. T., Daugherty, C. Z., Koenig, L., Yu, K., et al. (2017) · Science · doi:10.1126/science.aaf0683 · Cited by 1,015
Self-citationSystemic Immunity Is Required for Effective Cancer Immunotherapy
Spitzer, M. H., Carmi, Y., Reticker-Flynn, N. E., Kwek, S. S., Madhireddy, D., Martins, M. M., Gherardini, P. F., Prestwood, T. R., Chabon, J., Bendall, S. C., et al. (2017) · Cell · doi:10.1016/j.cell.2016.12.022 · Cited by 963
TIM3 comes of age as an inhibitory receptor
Wolf, Y., Anderson, A. C., & Kuchroo, V. K. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0224-6 · Cited by 959
Acquired Resistance to Immune Checkpoint Inhibitors
Schoenfeld, A. J., & Hellmann, M. D. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.03.017 · Cited by 991
Cancer nanomedicine for combination cancer immunotherapy
Nam, J., Son, S., Park, K. S., Zou, W., Shea, L. D., & Moon, J. J. (2019) · Nature Reviews Materials · doi:10.1038/s41578-019-0108-1 · Cited by 955
Kamphorst, A. O., Pillai, R. N., Yang, S., Nasti, T. H., Akondy, R. S., Wieland, A., Sica, G. L., Yu, K., Koenig, L., Patel, N. T., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1705327114 · Cited by 854
Self-citationTOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection
Alfei, F., Kanev, K., Hofmann, M., Wu, M., Ghoneim, H. E., Roelli, P., Utzschneider, D. T., von Hoesslin, M., Cullen, J. G., Fan, Y., et al. (2019) · Nature · doi:10.1038/s41586-019-1326-9 · Cited by 930
NR4A transcription factors limit CAR T cell function in solid tumours
Chen, J., López-Moyado, I. F., Seo, H., Lio, C.-W. J., Hempleman, L. J., Sekiya, T., Yoshimura, A., Scott-Browne, J. P., & Rao, A. (2019) · Nature · doi:10.1038/s41586-019-0985-x · Cited by 874
An intra-tumoral niche maintains and differentiates stem-like CD8 T cells
Jansen, C. S., Prokhnevska, N., Master, V. A., Sanda, M. G., Carlisle, J. W., Bilen, M. A., Cardenas, M. A., Wilkinson, S. C., Lake, R. G., Sowalsky, A. G., et al. (2019) · Nature · doi:10.1038/s41586-019-1836-5 · Cited by 826
Self-citationSeo, H., Chen, J., González-Avalos, E., Samaniego-Castruita, D., Das, A., Wang, Y. H., López-Moyado, I. F., Georges, R. O., Zhang, W., Onodera, A., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1905675116 · Cited by 808
Xu, S., Chaudhary, O., Rodríguez-Morales, P., Sun, X., Chen, D., Zappasodi, R., Xu, Z. Z., Pinto, A. F. M., Williams, A. E., Schulze, I., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.05.003 · Cited by 834
De Novo Epigenetic Programs Inhibit PD-1 Blockade-Mediated T Cell Rejuvenation
Ghoneim, H. E., Fan, Y., Moustaki, A., Abdelsamed, H. A., Dash, P., Dogra, P., Carter, R., Awad, W., Neale, G. A. M., Thomas, P. G., et al. (2017) · Cell · doi:10.1016/j.cell.2017.06.007 · Cited by 808
The Next Decade of Immune Checkpoint Therapy
Sharma, P., Siddiqui, B. A., Anandhan, S., Yadav, S. S., Subudhi, S. K., Gao, J., Goswami, S., & Allison, J. P. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1680 · Cited by 750
Peripheral T cell expansion predicts tumour infiltration and clinical response
Wu, T. D., Madireddi, S., de Almeida, P. E., Banchereau, R., Chen, Y.-J. J., Chitre, A. S., Chiang, E. Y., Iftikhar, H., O’Gorman, W. E., Au-Yeung, A., et al. (2020) · Nature · doi:10.1038/s41586-020-2056-8 · Cited by 770
Li, J., Byrne, K. T., Yan, F., Yamazoe, T., Chen, Z., Baslan, T., Richman, L. P., Lin, J., Sun, Y. H., Rech, A. J., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.06.006 · Cited by 746
TCF-1-centered transcriptional network drives an effector versus exhausted CD8 T cell-fate decision
Chen, Z., Ji, Z., Ngiow, S. F., Manne, S., Cai, Z., Huang, A. C., Johnson, J., Staupe, R. P., Bengsch, B., Xu, C., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.09.013 · Cited by 709
Chow, M. T., Ozga, A. J., Servis, R. L., Frederick, D. T., Lo, J. A., Fisher, D. E., Freeman, G. J., Boland, G. M., & Luster, A. D. (2019) · Immunity · doi:10.1016/j.immuni.2019.04.010 · Cited by 716
“Previous studies demonstrated that terminally exhausted CD8+ T cells upregulate their expression of granzyme B (Im et al., 2016; Utzschneider et al., 2016).”
Self-citationCheckpoint Blockade Immunotherapy Induces Dynamic Changes in PD-1-CD8+ Tumor-Infiltrating T Cells
Kurtulus, S., Madi, A., Escobar, G., Klapholz, M., Nyman, J., Christian, E., Pawlak, M., Dionne, D., Xia, J., Rozenblatt-Rosen, O., et al. (2019) · Immunity · doi:10.1016/j.immuni.2018.11.014 · Cited by 636
Hudson, W. H., Gensheimer, J., Hashimoto, M., Wieland, A., Valanparambil, R. M., Li, P., Lin, J.-X., Konieczny, B. T., Im, S. J., Freeman, G. J., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.11.002 · Cited by 656
Self-citationLocation, location, location: Tissue resident memory T cells in mice and humans
Szabo, P. A., Miron, M., & Farber, D. L. (2019) · Science Immunology · doi:10.1126/sciimmunol.aas9673 · Cited by 651
CD8 T Cell Exhaustion in Chronic Infection and Cancer: Opportunities for Interventions
Hashimoto, M., Kamphorst, A. O., Im, S. J., Kissick, H. T., Pillai, R. N., Ramalingam, S. S., Araki, K., & Ahmed, R. (2018) · Annual Review of Medicine · doi:10.1146/annurev-med-012017-043208 · Cited by 674
Self-citationZander, R., Schauder, D., Xin, G., Nguyen, C. P., Wu, X., Zajac, A. J., & Cui, W. (2019) · Immunity · doi:10.1016/j.immuni.2019.10.009 · Cited by 660
Targeting the epigenetic regulation of antitumour immunity
Hogg, S. J., Beavis, P. A., Dawson, M. A., & Johnstone, R. W. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0077-5 · Cited by 665
The TCF1-Bcl6 axis counteracts type I interferon to repress exhaustion and maintain T cell stemness
Wu, T., Ji, Y., Moseman, E. A., Xu, H. C., Manglani, M., Kirby, M., Anderson, S. M., Handon, R., Kenyon, E., Elkahloun, A. G., et al. (2016) · Science Immunology · doi:10.1126/sciimmunol.aai8593 · Cited by 632
T memory stem cells in health and disease
Gattinoni, L., Speiser, D. E., Lichterfeld, M. D., & Bonini, C. (2017) · Nature Medicine · doi:10.1038/nm.4241 · Cited by 648
Transient rest restores functionality in exhausted CAR-T cells through epigenetic remodeling
Weber, E. W., Parker, K. R., Sotillo, E., Lynn, R. C., Anbunathan, H., Lattin, J., Good, Z., Belk, J. A., Dániel, B., Klysz, D. D., et al. (2021) · Science · doi:10.1126/science.aba1786 · Cited by 653
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
The Tumor Microenvironment in the Response to Immune Checkpoint Blockade Therapies
Petitprez, F., Meylan, M., de Reyniès, A., Sautès‐Fridman, C., & Fridman, W. H. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00784 · Cited by 621
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
Combination Cancer Therapy with Immune Checkpoint Blockade: Mechanisms and Strategies
Patel, S. A., & Minn, A. J. (2018) · Immunity · doi:10.1016/j.immuni.2018.03.007 · Cited by 587
Single-cell RNA-seq reveals TOX as a key regulator of CD8+ T cell persistence in chronic infection
Yao, C., Sun, H.-W., Lacey, N. E., Ji, Y., Moseman, E. A., Shih, H.-Y., Heuston, E. F., Kirby, M., Anderson, S., Cheng, J., et al. (2019) · Nature Immunology · doi:10.1038/s41590-019-0403-4 · Cited by 549
Phenotype, specificity and avidity of antitumour CD8+ T cells in melanoma
Oliveira, G., Stromhaug, K., Klaeger, S., Kula, T., Frederick, D. T., Le, P. M., Forman, J., Huang, T., Li, S., Zhang, W., et al. (2021) · Nature · doi:10.1038/s41586-021-03704-y · Cited by 569
IL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor Progression
Sadik, A., Patterson, L. F. S., Öztürk, S., Mohapatra, S. R., Panitz, V., Secker, P. F., Pfänder, P., Loth, S., Salem, H., Prentzell, M. T., et al. (2020) · Cell · doi:10.1016/j.cell.2020.07.038 · Cited by 585
T cell stemness and dysfunction in tumors are triggered by a common mechanism
Vodnala, S. K., Eil, R., Kishton, R. J., Sukumar, M., Yamamoto, T. N., Ha, N.-H., Lee, P.-H., Shin, M., Patel, S. J., Yu, Z., et al. (2019) · Science · doi:10.1126/science.aau0135 · Cited by 552
The foundations of immune checkpoint blockade and the ipilimumab approval decennial
Korman, A. J., Garrett-Thomson, S. C., & Lönberg, N. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00345-8 · Cited by 572
Epigenetic therapy in immune-oncology
Jones, P. A., Ohtani, H., Chakravarthy, A., & Carvalho, D. D. D. (2019) · Nature reviews. Cancer · doi:10.1038/s41568-019-0109-9 · Cited by 559
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 569
Dynamics and specificities of T cells in cancer immunotherapy
Oliveira, G., & Wu, C. J. (2023) · Nature reviews. Cancer · doi:10.1038/s41568-023-00560-y · Cited by 574
VEGF-C-driven lymphatic drainage enables immunosurveillance of brain tumours
Song, E., Mao, T., Dong, H., Boisserand, L. S. B., Antila, S., Bosenberg, M., Alitalo, K. K., Thomas, J., & Iwasaki, A. (2020) · Nature · doi:10.1038/s41586-019-1912-x · Cited by 536
Understanding subset diversity in T cell memory
Jameson, S. C., & Masopust, D. (2018) · Immunity · doi:10.1016/j.immuni.2018.02.010 · Cited by 523
Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)
Cossarizza, A., Chang, H., Radbruch, A., Abrignani, S., Addo, R., Akdis, M., Andrä, I., Andreata, F., Annunziato, F., Arranz, E., et al. (2021) · European Journal of Immunology · doi:10.1002/eji.202170126 · Cited by 531
Epigenetic control of CD8+ T cell differentiation
Henning, A. N., Roychoudhuri, R., & Restifo, N. P. (2018) · Nature reviews. Immunology · doi:10.1038/nri.2017.146 · Cited by 518
Progressive immune dysfunction with advancing disease stage in renal cell carcinoma
Braun, D. A., Street, K., Burke, K. P., Cookmeyer, D. L., Denize, T., Pedersen, C. B., Gohil, S. H., Schindler, N. R., Pomerance, L., Hirsch, L., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.02.013 · Cited by 524
Self-citationMan, K., Gabriel, S. S., Liao, Y., Gloury, R., Preston, S., Henstridge, D. C., Pellegrini, M., Zehn, D., Berberich‐Siebelt, F., Febbraio, M. A., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.11.021 · Cited by 503
Type I Interferon in Chronic Virus Infection and Cancer
Snell, L. M., McGaha, T. L., & Brooks, D. G. (2017) · Trends in Immunology · doi:10.1016/j.it.2017.05.005 · Cited by 490
Huang, Q., Wu, X., Wang, Z., Chen, X., Wang, L., Lu, Y., Xiong, D., Liu, Q., Tian, Y., Lin, H., et al. (2022) · Cell · doi:10.1016/j.cell.2022.09.020 · Cited by 486
Recent Advances in Targeting CD8 T-Cell Immunity for More Effective Cancer Immunotherapy
Durgeau, A., Virk, Y., Corgnac, S., & Mami‐Chouaib, F. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00014 · Cited by 507
Katzenelenbogen, Y., Sheban, F., Yalin, A., Yofe, I., Svetlichnyy, D., Jaitin, D. A., Bornstein, C., Moshe, A., Keren-Shaul, H., Cohen, M., et al. (2020) · Cell · doi:10.1016/j.cell.2020.06.032 · Cited by 498
CD8+ T Cell Exhaustion in Cancer
Dolina, J. S., Budimir, N., Thomas, G. D., & Salek‐Ardakani, S. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.715234 · Cited by 504
Saravia, J., Chapman, N. M., & Chi, H. (2019) · Cellular & Molecular Immunology · doi:10.1038/s41423-019-0220-6 · Cited by 489
CXCR6 positions cytotoxic T cells to receive critical survival signals in the tumor microenvironment
Di Pilato, M., Kfuri-Rubens, R., Pruessmann, J. N., Ozga, A. J., Messemaker, M., Cadilha, B. L., Sivakumar, R., Cianciaruso, C., Warner, R. D., Marangoni, F., et al. (2021) · Cell · doi:10.1016/j.cell.2021.07.015 · Cited by 488
Self-citationCui, C., Wang, J., Fagerberg, E., Chen, P.-M., Connolly, K. A., Damo, M., Cheung, J. F., Mao, T., Askari, A. S., Chen, S., et al. (2020) · Cell · doi:10.1016/j.cell.2021.11.007 · Cited by 493
Role of PD-1 during effector CD8 T cell differentiation
Ahn, E., Araki, K., Hashimoto, M., Li, W., Riley, J. L., Cheung, J., Sharpe, A. H., Freeman, G. J., Irving, B. A., & Ahmed, R. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1718217115 · Cited by 486
Self-citationPrecursor exhausted T cells: key to successful immunotherapy?
Kallies, A., Zehn, D., & Utzschneider, D. T. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-019-0223-7 · Cited by 483
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
Metabolic and epigenetic regulation of T-cell exhaustion
Franco, F., Jaccard, A., Romero, P. J., Yu, Y.-R., & Ho, P. (2020) · Nature Metabolism · doi:10.1038/s42255-020-00280-9 · Cited by 479
Beyond immune checkpoint blockade: emerging immunological strategies
Kubli, S. P., Berger, T., Araújo, D. V., Siu, L. L., & Mak, T. W. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00155-y · Cited by 465
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 507
Genomic correlates of response to immune checkpoint blockade
Keenan, T. E., Burke, K. P., & Van Allen, E. M. (2019) · Nature Medicine · doi:10.1038/s41591-019-0382-x · Cited by 448
PD-L1 expression by dendritic cells is a key regulator of T-cell immunity in cancer
Oh, S. A., Wu, D.-C., Cheung, J., Navarro, A., Xiong, H., Cubas, R. A., Tótpál, K., Chiu, H. H., Wu, Y., Comps‐Agrar, L., et al. (2020) · Nature Cancer · doi:10.1038/s43018-020-0075-x · Cited by 466
Rahim, M. K., Okholm, T. L. H., Jones, K. B., McCarthy, E. E., Liu, C. C., Yee, J. L., Tamaki, S. J., Marquez, D. M., Tenvooren, I., Wai, K., et al. (2023) · Cell · doi:10.1016/j.cell.2023.02.021 · Cited by 455
Targeting REGNASE-1 programs long-lived effector T cells for cancer therapy
Wei, J., Long, L., Zheng, W., Dhungana, Y., Lim, S. A., Guy, C. S., Wang, Y., Wang, Y., Qian, C., Xu, B., et al. (2019) · Nature · doi:10.1038/s41586-019-1821-z · Cited by 447
Liu, B., Hu, X., Feng, K., Gao, R., Xue, Z., Zhang, S., Zhang, Y., Corse, E., Hu, Y., Han, W., et al. (2021) · Nature Cancer · doi:10.1038/s43018-021-00292-8 · Cited by 473
Metabolic reprogramming of terminally exhausted CD8+ T cells by IL-10 enhances anti-tumor immunity
Guo, Y., Xie, Y., Gao, M., Zhao, Y., Franco, F., Wenes, M., Siddiqui, I., Bevilacqua, A., Wang, H., Yang, H., et al. (2021) · Nature Immunology · doi:10.1038/s41590-021-00940-2 · Cited by 455
Hwang, W. L., Jagadeesh, K. A., Guo, J. A., Hoffman, H. I., Yadollahpour, P., Reeves, J. W., Mohan, R., Drokhlyansky, E., Van Wittenberghe, N., Ashenberg, O., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01134-8 · Cited by 426
Magen, A., Hamon, P., Fiaschi, N., Soong, B. Y., Park, M. D., Mattiuz, R., Humblin, E., Troncoso, L., D’souza, D., Dawson, T., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02345-0 · Cited by 429
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 429
Lactate increases stemness of CD8 + T cells to augment anti-tumor immunity
Feng, Q., Liu, Z., Yu, X., Huang, T., Chen, J., Wang, J., Wilhelm, J., Li, S., Song, J., Li, W., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32521-8 · Cited by 430
TIGIT: A Key Inhibitor of the Cancer Immunity Cycle
Manieri, N. A., Chiang, E. Y., & Grogan, J. L. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.10.002 · Cited by 414
Connolly, K. A., Kuchroo, M. R., Venkat, A., Khatun, A., Wang, J., William, I., Hornick, N. I., Fitzgerald, B., Damo, M., Kasmani, M. Y., et al. (2021) · Science Immunology · doi:10.1126/sciimmunol.abg7836 · Cited by 415
Successful and Maladaptive T Cell Aging
Goronzy, J. J., & Weyand, C. M. (2017) · Immunity · doi:10.1016/j.immuni.2017.03.010 · Cited by 362
Metadata
- Authors
- Im, S. J., Hashimoto, M., Gerner, M. Y., Lee, J., Kissick, H. T., Burger, M. C., Shan, Q., Hale, J. S., Lee, J., Nasti, T. H., Sharpe, A. H., Freeman, G. J., Germain, R. N., Nakaya, H. I., Xue, H.-H., & Ahmed, R.
- Affiliations
- Emory University (US)
- National Institutes of Health (US)
- University of Iowa (US)
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Universidade de São Paulo (BR)
- Corresponding author
- Ahmed, Rafi
- ORCID
- Venue
- Nature
- Published
- 2016-08-02
- Volume
- 537
- Issue
- 7620
- Pages
- 417-421
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5297183
- OpenAlex
- W2506616866
- Cited by
- 2,070
- References
- 37
- Citations by year
- 2026: 224 · 2025: 245 · 2024: 268 · 2023: 264 · 2022: 248 · 2021: 252 · 2020: 223 · 2019: 154 · 2018: 101 · 2017: 75 · 2016: 13
- FWCI
- 69.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health (n01ai30048-10-0-1)
- National Institute of Allergy and Infectious Diseases (N01 AI030048, P01AI080192, P01AI056299, R01AI030048, R01AI121080, R01AI112579)
- 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 › Virology › HIV Research and Treatment
- Keywords
- CD8+ T cells, PD-1, T cell exhaustion, lymphocytic choriomeningitis virus, chronic viral infection, B cell follicles, T follicular helper cells, PD-L1 blockade, anti-PD-1 therapy, HIV, virus control, costimulatory molecules
- MeSH terms
- Cell Self Renewal, Animals, Cell Differentiation, Female, T-Lymphocytes, Helper-Inducer, Hematopoietic Stem Cells, Immunotherapy, Lymphocytic Choriomeningitis, Lymphocytic choriomeningitis virus, T-Lymphocyte Subsets, CD28 Antigens, CD8-Positive T-Lymphocytes, Cell Proliferation, Mice, Hepatocyte Nuclear Factor 1-alpha, Inducible T-Cell Co-Stimulator Protein, Programmed Cell Death 1 Receptor
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
