Cited by 2,087Cancer Immunotherapy and BiomarkersT-cell and B-cell ImmunologyImmunotherapy and Immune Responses

The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.

Subsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade

Open access

Miller, Brian C., Sen, Debattama R., Al Abosy, Rose, Bi, Kevin, Virkud, Yamini V., LaFleur, Martin W., Yates, Kathleen B., Lako, Ana, Felt, Kristen, Naik, Girish S., Manos, Michael, Gjini, Evisa, Kuchroo, Juhi R., Ishizuka, Jeffrey J., Collier, Jenna L., Griffin, Gabriel K., Maleri, Seth, Comstock, Dawn E., Weiss, Sarah A., Brown, Flavian D., Panda, Arpit, Zimmer, Margaret D., Manguso, Robert T., Hodi, F. Stephen, Rodig, Scott J., Sharpe, Arlene H., Haining, W. Nicholas·2019·Nature Immunology

DOI 10.1038/s41590-019-0312-6PMC PMC6673650

Open this paper in CoChat — free account

Abstract

T cell dysfunction is a hallmark of many cancers, but the basis for T cell dysfunction and the mechanisms by which antibody blockade of the inhibitory receptor PD-1 (anti-PD-1) reinvigorates T cells are not fully understood. Here we show that such therapy acts on a specific subpopulation of exhausted CD8+ tumor-infiltrating lymphocytes (TILs). Dysfunctional CD8+ TILs possess canonical epigenetic and transcriptional features of exhaustion that mirror those seen in chronic viral infection. Exhausted CD8+ TILs include a subpopulation of 'progenitor exhausted' cells that retain polyfunctionality, persist long term and differentiate into 'terminally exhausted' TILs. Consequently, progenitor exhausted CD8+ TILs are better able to control tumor growth than are terminally exhausted T cells. Progenitor exhausted TILs can respond to anti-PD-1 therapy, but terminally exhausted TILs cannot. Patients with melanoma who have a higher percentage of progenitor exhausted cells experience a longer duration of response to checkpoint-blockade therapy. Thus, approaches to expand the population of progenitor exhausted CD8+ T cells might be an important component of improving the response to checkpoint blockade.

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 · 10.1038/s41590-019-0312-6

Cites

53 of 53 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?

Self-check

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

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

Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
Spatial reconstruction of single-cell gene expression data
Satija, R., Farrell, J. A., Gennert, D., Schier, A. F., & Regev, A. (2015) · Nature Biotechnology · doi:10.1038/nbt.3192 · Cited by 7,055
PD-1 blockade induces responses by inhibiting adaptive immune resistance
Tumeh, P. C., Harview, C. L., Yearley, J. H., Shintaku, I. P., Taylor, E. J. M., Robert, L., Chmielowski, B., Spasic, M., Henry, G., Ciobanu, V., et al. (2014) · Nature · doi:10.1038/nature13954 · Cited by 6,609
Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position
Buenrostro, J. D., Giresi, P. G., Zaba, L. C., Chang, H. Y., & Greenleaf, W. J. (2013) · Nature Methods · doi:10.1038/nmeth.2688 · Cited by 6,422
Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma
Snyder, A., Makarov, V., Merghoub, T., Yuan, J., Zaretsky, J. M., Desrichard, A., Walsh, L. A., Postow, M. A., Wong, P., Ho, T. S., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1406498 · Cited by 4,286
T cell exhaustion
Wherry, E. J. (2011) · Nature Immunology · doi:10.1038/ni.2035 · Cited by 4,062
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-citation
Control of Viremia in Simian Immunodeficiency Virus Infection by CD8 + Lymphocytes
Schmitz, J. E., Kuroda, M. J., Santra, S., Sasseville, V. G., Simon, M. A., Lifton, M. A., Rácz, P., Tenner‐Racz, K., Dalesandro, M. R., Scallon, B. J., et al. (1999) · Science · doi:10.1126/science.283.5403.857 · Cited by 2,167
Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
Wherry, E. J., Ha, S.-J., Kaech, S. M., Haining, W. N., Sarkar, S., Kalia, V., Subramaniam, S., Blattman, J. N., Barber, D. L., & Ahmed, R. (2007) · Immunity · doi:10.1016/j.immuni.2007.09.006 · Cited by 2,103
Self-citation
Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity
Sakuishi, K., Apetoh, L., Sullivan, J. M., Blazar, B. R., Kuchroo, V. K., & Anderson, A. C. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20100643 · Cited by 2,072

Show all 53 references

Sorted by citations

Items 201–300 of 1,002

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
Dendrobium officinale polysaccharides alleviate colon tumorigenesis via restoring intestinal barrier function and enhancing anti-tumor immune response
Liang, J., Li, H., Chen, J., He, L., Du, X., Zhou, L., Xiong, Q., Lai, X., Yang, Y., Huang, S. M., et al. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.104417 · Cited by 150
Exploring Markers of Exhausted CD8 T Cells to Predict Response to Immune Checkpoint Inhibitor Therapy for Hepatocellular Carcinoma
Hsu, C., Ou, D., Bai, L., Chen, C., Lin, L., Huang, S.-F. K., Cheng, A., Jeng, Y., & Hsu, C. (2021) · Liver Cancer · doi:10.1159/000515305 · Cited by 151
CAF-induced physical constraints controlling T cell state and localization in solid tumours
Arpinati, L., Carradori, G., & Scherz‐Shouval, R. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-024-00740-4 · Cited by 162
Spatial maps of T cell receptors and transcriptomes reveal distinct immune niches and interactions in the adaptive immune response
Liu, S., Iorgulescu, J. B., Li, S., Borji, M., Barrera, I., Shanmugam, V., Lyu, H., Morriss, J. W., Garcia, Z. N., Murray, E. M., et al. (2022) · Immunity · doi:10.1016/j.immuni.2022.09.002 · Cited by 148
Detecting Tumor Antigen-Specific T Cells via Interaction-Dependent Fucosyl-Biotinylation
Liu, Z., Li, J. P., Chen, M., Wu, M., Shi, Y., Li, W., Teijaro, J. R., & Wu, P. (2020) · Cell · doi:10.1016/j.cell.2020.09.048 · Cited by 148
Intratumoral CD103+ CD8+ T cells predict response to PD-L1 blockade
Banchereau, R., Chitre, A. S., Scherl, A., Wu, T. D., Patil, N. S., de Almeida, P. E., Kadel, E. E., Madireddi, S., Au‐Yeung, A., Takahashi, C., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-002231 · Cited by 153
Neuropilin-1: a checkpoint target with unique implications for cancer immunology and immunotherapy
Chuckran, C. A., Liu, C., Bruno, T. C., Workman, C. J., & Vignali, D. A. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-000967 · Cited by 147
Tfh-cell-derived interleukin 21 sustains effector CD8+ T cell responses during chronic viral infection
Zander, R., Kasmani, M. Y., Yao, C., Topchyan, P., Shen, J., Zheng, S., Burns, R., Ingram, J. T., Cui, C., Joshi, N. S., et al. (2022) · Immunity · doi:10.1016/j.immuni.2022.01.018 · Cited by 143
Non-terminally exhausted tumor-resident memory HBV-specific T cell responses correlate with relapse-free survival in hepatocellular carcinoma
Cheng, Y., Gunasegaran, B., Singh, H. D., Dutertre, C.-A., Loh, C. Y., Lim, J. Q., Crawford, J. C., Lee, H. K., Zhang, X., Lee, B., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.06.013 · Cited by 142
A peripheral immune signature of responsiveness to PD-1 blockade in patients with classical Hodgkin lymphoma
Cader, F. Z., Hu, X. S., Goh, W. L., Wienand, K., Ouyang, J., Mandato, E., Redd, R. A., Lawton, L. N., Chen, P.-H., Weirather, J. L., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-1006-1 · Cited by 145
Self-citation
PD-1 blockade restores helper activity of tumor-infiltrating, exhausted PD-1hiCD39+ CD4 T cells
Balança, C.-C., Salvioni, A., Scarlata, C., Michelas, M., Gomez‐Roca, C., Gomez‐Roca, C., Sarradin, V., Tosolini, M., Valle, C., Pont, F., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.142513 · Cited by 166
Hallmarks of Resistance to Immune-Checkpoint Inhibitors
Karasarides, M., Cogdill, A. P., Robbins, P. B., Bowden, M., Burton, E. M., Butterfield, L. H., Cesano, A., Hammer, C., Haymaker, C., Horak, C. E., et al. (2022) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-20-0586 · Cited by 154
Comparative analysis of cell–cell communication at single-cell resolution
Wilk, A. J., Shalek, A. K., Holmes, S., & Blish, C. A. (2023) · Nature Biotechnology · doi:10.1038/s41587-023-01782-z · Cited by 146
Trifluridine/Tipiracil plus Oxaliplatin Improves PD-1 Blockade in Colorectal Cancer by Inducing Immunogenic Cell Death and Depleting Macrophages
Limagne, E., Thibaudin, M., Nuttin, L., Spill, A., Dérangère, V., Fumet, J.-D., Amellal, N., Peranzoni, E., Cattan, V., & Ghiringhelli, F. (2019) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-19-0228 · Cited by 146
Cell Therapy With TILs: Training and Taming T Cells to Fight Cancer
Kumar, A., Watkins, R., & Vilgelm, A. E. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.690499 · Cited by 149
The Role of Cytokines in Predicting the Response and Adverse Events Related to Immune Checkpoint Inhibitors
Wang, M., Zhai, X., Li, J., Guan, J., Xu, S., Li, Y., & Zhu, H. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.670391 · Cited by 143
Advances and prospects of biomarkers for immune checkpoint inhibitors
Yamaguchi, H., Hsu, J.-M., Sun, L., Wang, S., & Hung, M. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101621 · Cited by 152
Direct and Indirect Regulators of Epithelial–Mesenchymal Transition–Mediated Immunosuppression in Breast Carcinomas
Dongre, A., Rashidian, M., Eaton, E. N., Reinhardt, F., Thiru, P., Zagorulya, M., Nepal, S., Banaz, T., Martner, A., Spranger, S., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0603 · Cited by 146
Localization, tissue biology and T cell state — implications for cancer immunotherapy
Schenkel, J. M., & Pauken, K. E. (2023) · Nature reviews. Immunology · doi:10.1038/s41577-023-00884-8 · Cited by 144
Antigen-presenting cancer associated fibroblasts enhance antitumor immunity and predict immunotherapy response
Song, J.-Q., Wei, R.-Y., Liu, C.-C., Zhao, Z.-X., Liu, X.-J., Wang, Y.-N., Liu, F.-L., & Liu, X.-W. (2025) · Nature Communications · doi:10.1038/s41467-025-57465-7 · Cited by 151
TIGIT/CD226 Axis Regulates Anti-Tumor Immunity
Yeo, J., Ko, M., Lee, D.-H., Park, Y., & Jin, H. (2021) · Pharmaceuticals · doi:10.3390/ph14030200 · Cited by 138
The Complex Integration of T-cell Metabolism and Immunotherapy
Madden, M. Z., & Rathmell, J. C. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0569 · Cited by 140
The transcription factor IRF2 drives interferon-mediated CD8+ T cell exhaustion to restrict anti-tumor immunity
Lukhele, S., Abd-Rabbo, D., Guo, M., Shen, J., Elsaesser, H. J., Quevedo, R., Carew, M., Gadalla, R., Snell, L. M., Mahesh, L., et al. (2022) · Immunity · doi:10.1016/j.immuni.2022.10.020 · Cited by 136
T cell dysfunction and therapeutic intervention in cancer
Zebley, C. C., Zehn, D., Gottschalk, S. M., & Chi, H. (2024) · Nature Immunology · doi:10.1038/s41590-024-01896-9 · Cited by 145
The type 2 cytokine Fc–IL-4 revitalizes exhausted CD8+ T cells against cancer
Feng, B., Bai, Z., Zhou, X., Zhao, Y., Xie, Y., Huang, X., Liu, Y., Enbar, T., Li, R., Wang, Y., et al. (2024) · Nature · doi:10.1038/s41586-024-07962-4 · Cited by 138
Overcoming primary and acquired resistance to anti-PD-L1 therapy by induction and activation of tumor-residing cDC1s
Oba, T., Long, M. D., Keler, T., Marsh, H. C., Minderman, H., Abrams, S. I., Liu, S., & Ito, F. (2020) · Nature Communications · doi:10.1038/s41467-020-19192-z · Cited by 140
The B7:CD28 family and friends: Unraveling coinhibitory interactions
Burke, K. P., Chaudhri, A., Freeman, G. J., & Sharpe, A. H. (2024) · Immunity · doi:10.1016/j.immuni.2024.01.013 · Cited by 148
Self-citation
Reinvigorating exhausted CD8 + cytotoxic T lymphocytes in the tumor microenvironment and current strategies in cancer immunotherapy
Hossain, M. A., Liu, G., Dai, B., Si, Y., Yang, Q., Wazir, J., Birnbaumer, L., & Yang, Y. (2020) · Medicinal Research Reviews · doi:10.1002/med.21727 · Cited by 141
The current state and future of T-cell exhaustion research
Jenkins, E. M., Whitehead, T., Fellermeyer, M., Davis, S. J., & Sharma, S. (2023) · Oxford Open Immunology · doi:10.1093/oxfimm/iqad006 · Cited by 153
Bispecific dendritic-T cell engager potentiates anti-tumor immunity
Itai, Y. S., Barboy, O., Salomon, R., Bercovich, A., Xie, K., Winter, E. E., Shami, T., Porat, Z., Erez, N., Tanay, A., et al. (2024) · Cell · doi:10.1016/j.cell.2023.12.011 · Cited by 142
Bispecific PD1-IL2v and anti-PD-L1 break tumor immunity resistance by enhancing stem-like tumor-reactive CD8+ T cells and reprogramming macrophages
Tichet, M., Wullschleger, S., Chryplewicz, A., Fournier, N., Marcone, R., Kauzlaric, A., Homicskó, K., Deak, L. C., Umaña, P., Klein, C., et al. (2023) · Immunity · doi:10.1016/j.immuni.2022.12.006 · Cited by 140
Genetic ablation of PRDM1 in antitumor T cells enhances therapeutic efficacy of adoptive immunotherapy
Yoshikawa, T., Wu, Z., Inoue, S., Kasuya, H., Matsushita, H., Takahashi, Y., Kuroda, H., Hosoda, W., Suzuki, S., & Kagoya, Y. (2021) · Blood · doi:10.1182/blood.2021012714 · Cited by 134
The ectonucleotidase CD39 identifies tumor-reactive CD8+ T cells predictive of immune checkpoint blockade efficacy in human lung cancer
Chow, A. T., Uddin, F. Z., Liu, M., Dobrin, A., Nabet, B. Y., Mangarin, L. M. B., Lavin, Y., Rizvi, H. A., Tischfield, S. E., Quintanal-Villalonga, À., et al. (2022) · Immunity · doi:10.1016/j.immuni.2022.12.001 · Cited by 141
ARID1A suppresses R-loop-mediated STING-type I interferon pathway activation of anti-tumor immunity
Maxwell, M. B., Hom, M. S., Yi, J., Li, S., Rivera, S. A., Yu, J., Burns, M. J., McRae, H. M., Stevenson, B. T., Coakley, K. E., et al. (2024) · Cell · doi:10.1016/j.cell.2024.04.025 · Cited by 147
Interleukin-10 receptor signaling promotes the maintenance of a PD-1int TCF-1+ CD8+ T cell population that sustains anti-tumor immunity
Hanna, B. S., Cid, L. L., Iskar, M., Roessner, P. M., Klett, L. C., Wong, J., Paul, Y., Ioannou, N., Öztürk, S., Mack, N. L., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.11.004 · Cited by 137
LILRB4 suppresses immunity in solid tumors and is a potential target for immunotherapy
Sharma, N., Atolagbe, O. T., Ge, Z., & Allison, J. P. (2021) · The Journal of Experimental Medicine · doi:10.1084/jem.20201811 · Cited by 134
Dual checkpoint blockade of CD47 and PD-L1 using an affinity-tuned bispecific antibody maximizes antitumor immunity
Chen, S.-H., Dominik, P. K., Stanfield, J., Ding, S., Yang, W., Kurd, N. S., Llewellyn, R. A., Heyen, J. R. R., Wang, C., Melton, Z., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-003464 · Cited by 135
The Multifaceted Role of Tissue-Resident Memory T Cells
Christo, S. N., Park, S. L., Mueller, S. N., & Mackay, L. K. (2024) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101320-020220 · Cited by 148
Chronic type I interferon signaling promotes lipid-peroxidation-driven terminal CD8+ T cell exhaustion and curtails anti-PD-1 efficacy
Chen, W., Teo, J. M. N., Yau, S. W., Wong, M. Y., Lok, C., Che, C., Javed, A., Huang, Y., Ma, S., & Ling, G. S. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111647 · Cited by 142
CDK4/6 Inhibition Promotes Antitumor Immunity through the Induction of T-cell Memory
Lelliott, E. J., Kong, I. Y., Zethoven, M., Ramsbottom, K. M., Martelotto, L. G., Meyran, D., Zhu, J. J., Costacurta, M., Kirby, L., Sandow, J. J., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1554 · Cited by 129
YY1 complex in M2 macrophage promotes prostate cancer progression by upregulating IL-6
Chen, S., Lǚ, K., Hou, Y., You, Z., Shu, C., Wei, X., Wu, T., Shi, N., Zhang, G., Wu, J., et al. (2023) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2022-006020 · Cited by 132
Expression of immune checkpoints and T cell exhaustion markers in early and advanced stages of colorectal cancer
Saleh, R., Taha, R. Z., Toor, S. M., Nair, V. S., Murshed, K., Khawar, M., Al‐Dhaheri, M., Petkar, M. A., Nada, M. A., & Elkord, E. (2020) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-020-02593-w · Cited by 128
Immunosuppressive CD10+ALPL+ neutrophils promote resistance to anti-PD-1 therapy in HCC by mediating irreversible exhaustion of T cells
Meng, Y., Ye, F., Nie, P., Zhao, Q., An, L., Wang, W., Qu, S., Shen, Z., Cao, Z., Zhang, X., et al. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.08.024 · Cited by 127
Integrated multi-omics profiling to dissect the spatiotemporal evolution of metastatic hepatocellular carcinoma
Sun, Y., Wu, P., Zhang, Z., Wang, Z., Zhou, K., Song, M., Ji, Y., Zang, F., Lou, L., Rao, K., et al. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.11.010 · Cited by 133
The tumor-draining lymph node as a reservoir for systemic immune surveillance
Delclaux, I., Ventre, K. S., Jones, D., & Lund, A. W. (2023) · Trends in cancer · doi:10.1016/j.trecan.2023.09.006 · Cited by 143
The Multifaceted Output of c-Jun Biological Activity: Focus at the Junction of CD8 T Cell Activation and Exhaustion
Papavassiliou, A. G., & Musti, A. M. (2020) · Cells · doi:10.3390/cells9112470 · Cited by 124
Lack of CD8 + T cell effector differentiation during priming mediates checkpoint blockade resistance in non–small cell lung cancer
Horton, B. L., Morgan, D. M., Momin, N., Zagorulya, M., Torres-Mejia, E., Bhandarkar, V., Wittrup, K. D., Love, J. C., & Spranger, S. (2021) · Science Immunology · doi:10.1126/sciimmunol.abi8800 · Cited by 124
Single cell analysis of cribriform prostate cancer reveals cell intrinsic and tumor microenvironmental pathways of aggressive disease
Wong, H. Y., Sheng, Q., Hesterberg, A. B., Croessmann, S., Rios, B. L., Giri, K. R., Jackson, J., Miranda, A. X., Watkins, E., Schaffer, K. R., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33780-1 · Cited by 131
Intratumoral TIGIT+ CD8+ T-cell infiltration determines poor prognosis and immune evasion in patients with muscle-invasive bladder cancer
Liu, Z., Zhou, Q., Wang, Z., Zhang, H., Zeng, H., Huang, Q., Chen, Y., Jiang, W., Lin, Z., Qu, Y., et al. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-000978 · Cited by 125
FcγR engagement reprograms neutrophils into antigen cross-presenting cells that elicit acquired anti-tumor immunity
Mysore, V., Culleré, X., Mears, J., Rosetti, F., Okubo, K., Liew, P. X., Zhang, F., Madera-Salcedo, I. K., Rosenbauer, F., Stone, R. M., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24591-x · Cited by 129
MHC class II-restricted antigen presentation is required to prevent dysfunction of cytotoxic T cells by blood-borne myeloids in brain tumors
Kilian, M., Sheinin, R., Tan, C. L., Friedrich, M., Krämer, C., Kaminitz, A., Sanghvi, K., Lindner, K. A. M., Chih, Y., Cichon, F., et al. (2023) · Cancer Cell · doi:10.1016/j.ccell.2022.12.007 · Cited by 124
Heterogeneity in tertiary lymphoid structure B-cells correlates with patient survival in metastatic melanoma
Lynch, K., Young, S. J., Meneveau, M. O., Wages, N. A., Engelhard, V. H., Slingluff, C. L., & Mauldin, I. S. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-002273 · Cited by 131
High endothelial venules in cancer: Regulation, function, and therapeutic implication
Vella, G., Hua, Y., & Bergers, G. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.02.002 · Cited by 132
STAT3 regulates CD8+ T cell differentiation and functions in cancer and acute infection
Sun, Q., Zhao, X., Li, R., Liu, D., Pan, B., Xie, B., Chi, X., Cai, D., Wei, P., Xu, W., et al. (2023) · The Journal of Experimental Medicine · doi:10.1084/jem.20220686 · Cited by 129
Preexisting tumor-resident T cells with cytotoxic potential associate with response to neoadjuvant anti–PD-1 in head and neck cancer
Oliveira, G., Egloff, A. M., Afeyan, A. B., Wolff, J. O., Zeng, Z., Chernock, R. D., Zhou, L., Messier, C. M., Lizotte, P. H., Pfaff, K. L., et al. (2023) · Science Immunology · doi:10.1126/sciimmunol.adf4968 · Cited by 130
Self-citation
PD-1+ stemlike CD8 T cells are resident in lymphoid tissues during persistent LCMV infection
Im, S. J., Konieczny, B. T., Hudson, W. H., Masopust, D., & Ahmed, R. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1917298117 · Cited by 124
Single cell analysis in head and neck cancer reveals potential immune evasion mechanisms during early metastasis
Quah, H. S., Cao, E. Y., Suteja, L., Li, C. H., Leong, H. S., Chong, F. T., Gupta, S., Arcinas, C., Ouyang, J. F., Ang, V., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37379-y · Cited by 126
A unified atlas of CD8 T cell dysfunctional states in cancer and infection
Pritykin, Y., van der Veeken, J., Pine, A. R., Zhong, Y., Şahin, M., Mažutis, L., Pe’er, D., Rudensky, A. Y., & Leslie, C. S. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.03.045 · Cited by 117
Generation of allogeneic CAR-NKT cells from hematopoietic stem and progenitor cells using a clinically guided culture method
Li, Y.-R., Zhou, Y., Yu, J., Kim, K. G., Li, M., Lee, D., Zhou, K., Chen, Y., Zhu, Y., Wang, Y.-C., et al. (2024) · Nature Biotechnology · doi:10.1038/s41587-024-02226-y · Cited by 131
Lesion-Level Response Dynamics to Programmed Cell Death Protein (PD-1) Blockade
Osorio, J. C., Arbour, K. C., Le, D. T., Durham, J. N., Plodkowski, A. J., Halpenny, D. F., Ginsberg, M. S., Sawan, P., Crompton, J. G., Yu, H. A., et al. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.19.00709 · Cited by 118
Sex-Biased T-cell Exhaustion Drives Differential Immune Responses in Glioblastoma
Lee, J., Nicosia, M., Hong, E. S., Silver, D. J., Li, C., Bayık, D., Watson, D. C., Lauko, A. J., Kay, K. E., Wang, S. Z., et al. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-0869 · Cited by 133
Integrative analysis of neuroblastoma by single-cell RNA sequencing identifies the NECTIN2-TIGIT axis as a target for immunotherapy
Wienke, J., Visser, L. L., Kholosy, W. M., Keller, K. M., Barisa, M., Poon, E., Munnings-Tomes, S., Himsworth, C., Calton, E. A., Rodríguez, A. I. E., et al. (2024) · Cancer Cell · doi:10.1016/j.ccell.2023.12.008 · Cited by 129
TDO2+ myofibroblasts mediate immune suppression in malignant transformation of squamous cell carcinoma
Hu, S., Lu, H., Xie, W., Wang, D., Shan, Z., Xing, X., Wang, X.-M., Fang, J., Dong, W., Dai, W., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci157649 · Cited by 129
TCR-independent CD137 (4-1BB) signaling promotes CD8+-exhausted T cell proliferation and terminal differentiation
Pichler, A., Carrié, N., Cuisinier, M., Ghazali, S., Voisin, A., Axisa, P., Tosolini, M., Mazzotti, C., Golec, D. P., Mahéo, S., et al. (2023) · Immunity · doi:10.1016/j.immuni.2023.06.007 · Cited by 124
Predictive biomarkers for response to immune checkpoint inhibition
Shum, B., Larkin, J., & Turajlic, S. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.03.036 · Cited by 118
Intratumoral follicular regulatory T cells curtail anti-PD-1 treatment efficacy
Eschweiler, S., Clarke, J. D., Ramírez-Suástegui, C., Panwar, B., Madrigal, A., Chee, S., Karydis, I., Woo, E. B. C., Alzetani, A., Elsheikh, S. E., et al. (2021) · Nature Immunology · doi:10.1038/s41590-021-00958-6 · Cited by 119
Single-cell analyses identify circulating anti-tumor CD8 T cells and markers for their enrichment
Pauken, K. E., Shahid, O., Lagattuta, K. A., Mahuron, K. M., Luber, J. M., Lowe, M. M., Huang, L., Delaney, C., Long, J. M., Fung, M. E., et al. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20200920 · Cited by 116
Self-citation
Improving CAR T-Cell Persistence
Pietrobon, V., Todd, L. A., Goswami, A., Stefanson, O., Yang, Z., & Marincola, F. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910828 · Cited by 124
TCR-T Immunotherapy: The Challenges and Solutions
Liu, Y., Yan, X., Zhang, F., Zhang, X., Tang, F., Han, Z., & Li, Y. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2021.794183 · Cited by 117
SOX17 enables immune evasion of early colorectal adenomas and cancers
Goto, N., Westcott, P. M. K., Goto, S., Imada, S., Taylor, M. S., Eng, G. M., Braverman, J., Deshpande, V., Jacks, T., Agudo, J., et al. (2024) · Nature · doi:10.1038/s41586-024-07135-3 · Cited by 122
Combination anti-PD-1 and anti-CTLA-4 therapy generates waves of clonal responses that include progenitor-exhausted CD8+ T cells
Wang, K., Coutifaris, P., Brocks, D., Wang, G., Azar, T., Solis, S., Nandi, A., Anderson, S., Han, N. A., Manne, S., et al. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.08.007 · Cited by 127
DNA hypermethylation during tuberculosis dampens host immune responsiveness
DiNardo, A. R., Rajapakshe, K., Nishiguchi, T., Mtetwa, G., Dlamini, Q., Kahari, J., Mahapatra, S., Kay, A., Gugu, M., Mace, E., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci134622 · Cited by 116
Type 1 conventional dendritic cells maintain and guide the differentiation of precursors of exhausted T cells in distinct cellular niches
Dähling, S., Mansilla, A. M., Knöpper, K., Grafen, A., Utzschneider, D. T., Ugur, M., Whitney, P. G., Bachem, A., Arampatzi, P., Imdahl, F., et al. (2022) · Immunity · doi:10.1016/j.immuni.2022.03.006 · Cited by 109
Therapeutic potential of CAR T cell in malignancies: A scoping review
Mehrabadi, A. Z., Ranjbar, R., Farzanehpour, M., Shahriary, A., Dorostkar, R., Hamidinejad, M. A., & Ghaleh, H. E. G. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112512 · Cited by 116
Cancer cells resistant to immune checkpoint blockade acquire interferon-associated epigenetic memory to sustain T cell dysfunction
Qiu, J., Xu, B., Ye, D., Ren, D., Wang, S., Benci, J. L., Xu, Y., Ishwaran, H., Beltra, J., Wherry, E. J., et al. (2023) · Nature Cancer · doi:10.1038/s43018-022-00490-y · Cited by 117
LAG-3 sustains TOX expression and regulates the CD94/NKG2-Qa-1b axis to govern exhausted CD8 T cell NK receptor expression and cytotoxicity
Ngiow, S. F., Manne, S., Huang, Y., Azar, T., Chen, Z., Mathew, D., Chen, Q., Khan, O., Wu, J. E., Alcalde, V., et al. (2024) · Cell · doi:10.1016/j.cell.2024.07.018 · Cited by 116
Self-citation
Single cell analysis reveals distinct immune landscapes in transplant and primary sarcomas that determine response or resistance to immunotherapy
Wisdom, A. J., Mowery, Y. M., Hong, C. S., Himes, J. E., Nabet, B. Y., Qin, X., Zhang, D., Chen, L., Fradin, H., Patel, R., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19917-0 · Cited by 113
Tumor microenvironmental signals reshape chromatin landscapes to limit the functional potential of exhausted T cells
Ford, B. R., Vignali, P., Rittenhouse, N., Scharping, N. E., Peralta, R. M., Lontos, K., Frisch, A. T., Delgoffe, G. M., & Poholek, A. C. (2022) · Science Immunology · doi:10.1126/sciimmunol.abj9123 · Cited by 112
Multiomics identifies metabolic subtypes based on fatty acid degradation allocating personalized treatment in hepatocellular carcinoma
Li, B., Li, Y., Zhou, H., Xu, Y., Cao, Y., Cheng, C., Peng, J., Li, H., Zhang, L., Su, K., et al. (2023) · Hepatology · doi:10.1097/hep.0000000000000553 · Cited by 110
Single-cell multiomics analysis reveals regulatory programs in clear cell renal cell carcinoma
Long, Z., Sun, C., Tang, M., Wang, Y., Ma, J., Yu, J., Wei, J., Ma, J., Wang, B., Xie, Q., et al. (2022) · Cell Discovery · doi:10.1038/s41421-022-00415-0 · Cited by 109
The aged tumor microenvironment limits T cell control of cancer
Chen, C.-Y., Jaiswal, S., Martínez, D., Yerinde, C., Ji, K. Y., Miranda, V., Fung, M. E., Weiss, S. A., Zschummel, M., Taguchi, K., et al. (2024) · Nature Immunology · doi:10.1038/s41590-024-01828-7 · Cited by 114
Self-citation
IL-15 Preconditioning Augments CAR T Cell Responses to Checkpoint Blockade for Improved Treatment of Solid Tumors
Giuffrida, L., Sek, K., Henderson, M. A., House, I. G., Lai, J., Chen, A. X. Y., Todd, K. L., Petley, E. V., Mardiana, S., Todorovski, I., et al. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.07.018 · Cited by 109
Cancer cell-intrinsic mechanisms driving acquired immune tolerance
Ghorani, E., Swanton, C., & Quezada, S. A. (2023) · Immunity · doi:10.1016/j.immuni.2023.09.004 · Cited by 116
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
Stem, Effector, and Hybrid States of Memory CD8+ T Cells
Lugli, E., Galletti, G., Boi, S. K., & Youngblood, B. (2019) · Trends in Immunology · doi:10.1016/j.it.2019.11.004 · Cited by 107
Role of the Orphan Nuclear Receptor NR4A Family in T-Cell Biology
Odagiu, L., May, J., Boulet, S., Baldwin, T. A., & Labrecque, N. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.624122 · Cited by 110
Modification of Extracellular Matrix Enhances Oncolytic Adenovirus Immunotherapy in Glioblastoma
Kiyokawa, J., Kawamura, Y., Ghouse, S. M., Acar, S., Barçın, E., Martínez‐Quintanilla, J., Martuza, R. L., Alemany, R., Rabkin, S. D., Shah, K., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-2400 · Cited by 106
Multimodal single-cell profiling of intrahepatic cholangiocarcinoma defines hyperactivated Tregs as a potential therapeutic target
Alvisi, G., Termanini, A., Soldani, C., Portale, F., Carriero, R., Pilipow, K., Costa, G., Polidoro, M. A., Franceschini, B., Malenica, I., et al. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.05.043 · Cited by 114
T STEM -like CAR-T cells exhibit improved persistence and tumor control compared with conventional CAR-T cells in preclinical models
Meyran, D., Zhu, J. J., Butler, J., Tantalo, D. G. M., Macdonald, S., Nguyen, T. N., Wang, M., Thio, N., D’Souza, C., Qin, V. M., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.abk1900 · Cited by 108
Cytokine-mediated CAR T therapy resistance in AML
Bhagwat, A. S., Torres, L., Shestova, O. E., Shestov, M., Mellors, P. W., Fisher, H. R., Farooki, S., Frost, B. F., Loken, M. R., Gaymon, A. L., et al. (2024) · Nature Medicine · doi:10.1038/s41591-024-03271-5 · Cited by 117
Evolution of cell therapy for renal cell carcinoma
Wang, Y., Suarez, E. R., Kastrunes, G. M., de Campos, N. S. P., Abbas, R., Pivetta, R. S., Murugan, N., Chalbatani, G. M., D’Andrea, V. D., & Marasco, W. A. (2024) · Molecular Cancer · doi:10.1186/s12943-023-01911-x · Cited by 110
Immunotherapy Goes Local: The Central Role of Lymph Nodes in Driving Tumor Infiltration and Efficacy
van Pul, K. M., Fransen, M. F., van de Ven, R., & de Gruijl, T. D. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.643291 · Cited by 105
Cell microparticles loaded with tumor antigen and resiquimod reprogram tumor-associated macrophages and promote stem-like CD8+ T cells to boost anti-PD-1 therapy
Zhang, X., Wei, Z., Yong, T., Li, S., Bie, N., Li, J., Li, X., Liu, H., Xu, H., Yan, Y., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-41438-9 · Cited by 112
Tertiary lymphoid structures and B cells determine clinically relevant T cell phenotypes in ovarian cancer
Kašíková, L., Raková, J., Hensler, M., Láníčková, T., Tománková, J., Pasulka, J., Drozenová, J., Mojžíšová, K., Fialová, A., Vosahlikova, S., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-46873-w · Cited by 111
Tissue-resident memory CD8 T cell diversity is spatiotemporally imprinted
Reina‐Campos, M., Monell, A., Ferry, A., Luna, V., Cheung, K. P., Galletti, G., Scharping, N. E., Takehara, K. K., Quon, S., Challita, P. P., et al. (2025) · Nature · doi:10.1038/s41586-024-08466-x · Cited by 111
High Endothelial Venules: A Vascular Perspective on Tertiary Lymphoid Structures in Cancer
Vella, G., Guelfi, S., & Bergers, G. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.736670 · Cited by 104
LSD1 inhibition sustains T cell invigoration with a durable response to PD-1 blockade
Liu, Y., Debo, B. M., Li, M., Shi, Z., Sheng, W., & Shi, Y. (2021) · Nature Communications · doi:10.1038/s41467-021-27179-7 · Cited by 109
Combined PD-L1/TGFβ blockade allows expansion and differentiation of stem cell-like CD8 T cells in immune excluded tumors
Castiglioni, A., Yang, Y., Williams, K., Gogineni, A., Lane, R. S., Wang, A. W., Shyer, J. A., Zhang, Z., Mittman, S., Gutierrez, A., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-40398-4 · Cited by 104
Memory T-Cell Heterogeneity and TerminologyPreprint
Muroyama, Y., & Wherry, E. J. (2021) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a037929 · Cited by 104

Authors: 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., Manos, M., Gjini, E., Kuchroo, J. R., Ishizuka, J. J., Collier, J. L., Griffin, G. K., Maleri, S., Comstock, D. E., Weiss, S. A., Brown, F. D., Panda, A., Zimmer, M. D., Manguso, R. T., Hodi, F. S., Rodig, S. J., Sharpe, A. H., & Haining, W. N.
Affiliations: Broad Institute (US)
Massachusetts General Hospital (US)
Dana-Farber Cancer Institute (US)
Brigham and Women's Hospital (US)
Corresponding author: Haining, W. Nicholas
ORCID: Miller, Brian C.
Sen, Debattama R.
Al Abosy, Rose
Bi, Kevin
Virkud, Yamini V.
LaFleur, Martin W.
Yates, Kathleen B.
Lako, Ana
Felt, Kristen
Naik, Girish S.
Manos, Michael
Gjini, Evisa
Kuchroo, Juhi R.
Ishizuka, Jeffrey J.
Collier, Jenna L.
Griffin, Gabriel K.
Comstock, Dawn E.
Weiss, Sarah A.
Zimmer, Margaret D.
Manguso, Robert T.
Hodi, F. Stephen
Rodig, Scott J.
Sharpe, Arlene H.
Haining, W. Nicholas
Venue: Nature Immunology
Publisher: Springer Science and Business Media LLC
Published: 2019-02-18
Volume: 20
Issue: 3
Pages: 326-336
ISSN: 1529-2908 (ISSN-L)
1529-2916
DOI: 10.1038/s41590-019-0312-6
PMC: PMC6673650
OpenAlex: W2913558101
Cited by: 2,087
References: 53
Citations by year: 2026: 319 · 2025: 334 · 2024: 358 · 2023: 300 · 2022: 276 · 2021: 269 · 2020: 176 · 2019: 55
FWCI: 81.19
Type: journal article
Language: en
Update notices: correction (2019-10-03)
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature Immunology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (KL2TR002542)
National Heart, Lung, and Blood Institute (T32HL007627)
National Cancer Institute (T32CA207021, T32CA009172)
National Institute of General Medical Sciences (T32GM007753)
National Institute of Allergy and Infectious Diseases (R01AI115712, K23AI130408, U19AI133524, P01AI056299)
National Center for Advancing Translational Sciences
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 › Immunotherapy and Immune Responses
Keywords: T cell exhaustion, CD8+ T cells, PD-1, anti-PD-1 therapy, immune checkpoint blockade, tumor-infiltrating lymphocytes, melanoma, T cell polyfunctionality, chronic viral infection, tumor control
MeSH terms: Animals, Female, Humans, Lymphocytic Choriomeningitis, Lymphocytic choriomeningitis virus, Melanoma, Experimental, Mice, Inbred C57BL, Lymphocyte Subsets, Lymphocytes, Tumor-Infiltrating, CD8-Positive T-Lymphocytes, Antibodies, Blocking, Mice, Congenic, Cell Line, Tumor, 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

Subsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks