Tumor-Specific T Cell Dysfunction Is a Dynamic Antigen-Driven Differentiation Program Initiated Early during Tumorigenesis
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CD8(+) T cells recognizing tumor-specific antigens are detected in cancer patients but are dysfunctional. Here we developed a tamoxifen-inducible liver cancer mouse model with a defined oncogenic driver antigen (SV40 large T-antigen) to follow the activation and differentiation of naive tumor-specific CD8(+) T (TST) cells after tumor initiation. Early during the pre-malignant phase of tumorigenesis, TST cells became dysfunctional, exhibiting phenotypic, functional, and transcriptional features similar to dysfunctional T cells isolated from late-stage human tumors. Thus, T cell dysfunction seen in advanced human cancers may already be established early during tumorigenesis. Although the TST cell dysfunctional state was initially therapeutically reversible, it ultimately evolved into a fixed state. Persistent antigen exposure rather than factors associated with the tumor microenvironment drove dysfunction. Moreover, the TST cell differentiation and dysfunction program exhibited features distinct from T cell exhaustion in chronic infections. Strategies to overcome this antigen-driven, cell-intrinsic dysfunction may be required to improve cancer immunotherapy.
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Adoptively transferred Tag-specific CD8+ T cells showed classic signs of exhaustion upon entering tumor-bearing livers.
“Profiling adoptively transferred SV40 large T cell antigen (Tag+)–specific CD8+ T cells indicated that Tag+ T cells followed classic signs of exhaustion upon entry into the tumor-bearing livers (fig. S2D) (19).”
From Bile acid synthesis impedes tumor-specific T cell responses during liver cancer (2025) · cites this paper as [19]
In Results, “Presence and Persistence of Antigen Dictates Tumor-Specific CD8+ T Cell Dysfunction in Solid Tumors” (page unavailable), adoptively transferred Tag-specific T cells localized to tumor-containing livers, then became increasingly dysfunctional, expressing inhibitory receptors and failing to produce effector cytokines. The source describes this as a process that develops over time, not as exhaustion already present upon entry; it also distinguishes tumor-associated dysfunction from exhaustion during chronic infection. (LLM, conf=0.85)
Experimental — accuracy not yet measuredTerminal Tex (Ttex) cells accumulate over time and respond poorly to immune checkpoint blockade therapies.
“Conversely, terminal Tex (Ttex) cells accumulate over time and respond poorly to ICB therapies8,11–13.”
From Proteotoxic stress response drives T cell exhaustion and immune evasion (2025) · cites this paper as [13]
The Results section, “Tumor-Specific T Cells Ultimately Enter a Fixed State of Dysfunction” (page unavailable), reports that later-stage tumor-specific T cells resisted PD-1/PD-L1 blockade. But the Results section comparing tumor dysfunction with viral exhaustion attributes accumulation of terminally exhausted cells over time to chronic viral infection and says tumor-specific cells followed a distinct differentiation pattern. The source therefore supports the poor-response point, not the unqualified accumulation claim. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe T cell immune response to HCC antigens is reportedly dysfunctional and unreactive to HCC.
“Indeed, the T cell immune response to HCC antigens is reportedly dysfunctional and unreactive to HCC55.”
From Tumor-specific cholinergic CD4+ T lymphocytes guide immunosurveillance of hepatocellular carcinoma (2023) · cites this paper as [55]
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PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989 · see citing works
Safety, activity, and immune correlates of anti–PD-1 antibody in cancer
Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200690 · Cited by 12,628 · see citing works
Signatures of mutational processes in human cancer
Initiative, A. P. C. G., Alexandrov, L. B., ICGC Breast Cancer Consortium, ICGC MMML-Seq Consortium, PedBrain, I., Nik-Zainal, S., Wedge, D. C., Aparicio, S. A. J. R., Behjati, S., Biankin, A. V., et al. (2013) · Nature · doi:10.1038/nature12477 · Cited by 9,660 · see citing works
Safety and activity of anti-PD-L1 antibody in patients with advanced cancer
Brahmer, J. R., Tykodi, S. S., Chow, L. Q. M., Hwu, W.-J., Topalian, S. L., Hwu, P., Drake, C. G., Camacho, L. H., Kauh, J., Odunsi, K., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200694 · Cited by 7,945 · cited 1× · see citing works
“…studies have demonstrated that blocking inhibitory receptors (checkpoint blockade) can mediate functional rescue of unresponsive T cells in chronic infection or tumors (Barber et al., 2006; Brahmer et al., 2012; Perez-Gracia et al., 2014; (A) Tamoxifen (Tam)-inducible ASTxCre-ERT2 tumor model.”
Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer
Rizvi, N. A., Hellmann, M. D., Snyder, A., Kvistborg, P., Makarov, V., Havel, J. J., Lee, W., Yuan, J., Wong, P., Ho, T. S., et al. (2015) · Science · doi:10.1126/science.aaa1348 · Cited by 7,802 · see citing works
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 · see citing works
Tumor-Associated Macrophages: From Mechanisms to Therapy
Noy, R., & Pollard, J. W. (2014) · Immunity · doi:10.1016/j.immuni.2014.06.010 · Cited by 4,089 · see citing works
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 3,960 · see citing works
Coordinated regulation of myeloid cells by tumours
Gabrilovich, D. I., Ostrand-Rosenberg, S., & Bronte, V. (2012) · Nature Reviews Immunology · doi:10.1038/nri3175 · Cited by 3,544 · see citing works
T cell receptor antagonist peptides induce positive selection.
Hogquist, K., Jameson, S., Heath, W., Howard, J. L., Bevan, M., & Carbone, F. (1994) · Cell · doi:10.1016/0092-8674(94)90169-4 · Cited by 3,252 · see citing works
T cell exclusion, immune privilege, and the tumor microenvironment
Joyce, J. A., & Fearon, D. T. (2015) · Science · doi:10.1126/science.aaa6204 · Cited by 2,494 · see citing works
The Polycomb group protein EZH2 directly controls DNA methylation
Viré, E., Brenner, C., Deplus, R., Blanchon, L., Fraga, M., Didelot, C., Morey, L., Van Eynde, A., Bernard, D., Vanderwinden, J.-M., et al. (2006) · Nature · doi:10.1038/nature04431 · Cited by 2,204 · see citing works
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 · see citing works
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 · see citing works
Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens
Gubin, M. M., Zhang, X., Schuster, H., Caron, E., Ward, J. P., Noguchi, T., Ivanova, Y., Hundal, J., Arthur, C. D., Krebber, W.-J., et al. (2014) · Nature · doi:10.1038/nature13988 · Cited by 1,974 · see citing works
Cancer Immunotherapy Based on Mutation-Specific CD4+ T Cells in a Patient with Epithelial Cancer
Tran, E., Turcotte, S., Gros, A., Robbins, P. F., Lu, Y., Dudley, M. E., Wunderlich, J. R., Somerville, R. P. T., Hogan, K., Hinrichs, C. S., et al. (2014) · Science · doi:10.1126/science.1251102 · Cited by 1,710 · see citing works
Transcriptional control of effector and memory CD8+ T cell differentiation
Kaech, S. M., & Cui, W. (2012) · Nature Reviews Immunology · doi:10.1038/nri3307 · Cited by 1,628 · see citing works
Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
Wherry, E. J., Ha, S., 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.2007.11.006 · Cited by 1,355 · see citing works
A p16 INK4a -Insensitive CDK4 Mutant Targeted by Cytolytic T Lymphocytes in a Human Melanoma
Wölfel, T., Hauer, M., Schneider, J., Serrano, M., Wölfel, C., Klehmann, E., Plaen, E. D., Hankeln, T., Büschenfelde, K. M. Z., & Beach, D. (1995) · Science · doi:10.1126/science.7652577 · Cited by 1,153 · see citing works
PD-1 identifies the patient-specific CD8+ tumor-reactive repertoire infiltrating human tumors
Gros, A., Robbins, P. F., Yao, X., Li, Y. F., Turcotte, S., Tran, E., Wunderlich, J. R., Mixon, A., Farid, S., Dudley, M. E., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci73639 · Cited by 1,113 · see citing works
Robbins, P. F., Lu, Y., El‐Gamil, M., Li, Y. F., Gross, C. A., Gartner, J. J., Lin, J., Teer, J. K., Cliften, P. F., Tycksen, E., et al. (2013) · Nature Medicine · doi:10.1038/nm.3161 · Cited by 1,074 · 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
Exhaustion of tumor-specific CD8+ T cells in metastases from melanoma patients
Baitsch, L., Baumgaertner, P., Devêvre, E., Raghav, S. K., Legat, A., Barba, L., Wieckowski, S., Bouzourene, H., Deplancke, B., Romero, P., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci46102 · Cited by 845 · see citing works
van Rooij, N., van Buuren, M. M., Philips, D., Velds, A., Toebes, M., Heemskerk, B., van Dijk, L. J. A., Behjati, S., Hilkmann, H., el Atmioui, D., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.47.7521 · Cited by 798 · see citing works
T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment
Crespo, J., Sun, H., Welling, T. H., Tian, Z., & Zou, W. (2013) · Current Opinion in Immunology · doi:10.1016/j.coi.2012.12.003 · Cited by 752 · see citing works
Tolerance and exhaustion: defining mechanisms of T cell dysfunction
Schietinger, A., & Greenberg, P. D. (2013) · Trends in Immunology · doi:10.1016/j.it.2013.10.001 · Cited by 677 · see citing works
Self-citationLinnemann, C., van Buuren, M. M., Bies, L., Verdegaal, E. M. E., Schotte, R., Calis, J. J. A., Behjati, S., Velds, A., Hilkmann, H., Atmioui, D. E., et al. (2014) · Nature Medicine · doi:10.1038/nm.3773 · Cited by 671 · see citing works
Vascular normalization in Rgs5-deficient tumours promotes immune destruction
Hamzah, J., Jugold, M., Kiessling, F. M., Rigby, P. J., Manzur, M., Marti, H. H., Rabie, T., Kaden, S., Gröne, H., Hämmerling, G. J., et al. (2008) · Nature · doi:10.1038/nature06868 · Cited by 565 · see citing works
Self-citationRobbins, P. F., El-Gamil, M., Li, Y. F., Kawakami, Y., Loftus, D., Appella, E., & Rosenberg, S. A. (1996) · The Journal of experimental medicine · doi:10.1084/jem.183.3.1185 · Cited by 550 · see citing works
Quigley, M. M., Pereyra, F., Nilsson, B., Porichis, F., Fonseca, C., Eichbaum, Q. G., Jülg, B. D., Jesneck, J. L., Brosnahan, K., Imam, S., et al. (2010) · Nature Medicine · doi:10.1038/nm.2232 · Cited by 505 · 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
The response of autologous T cells to a human melanoma is dominated by mutated neoantigens
Lennerz, V., Fatho, M., Gentilini, C., Frye, R. A., Lifke, A., Ferel, D., Wölfel, C., Huber, C., & Wölfel, T. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500090102 · Cited by 458 · see citing works
Sporadic immunogenic tumours avoid destruction by inducing T-cell tolerance
Willimsky, G., & Blankenstein, T. J. F. (2005) · Nature · doi:10.1038/nature03954 · Cited by 439 · see citing works
Youngblood, B., Oestreich, K. J., Ha, S., Duraiswamy, J., Akondy, R. S., West, E. E., Wei, Z., Lu, P., Austin, J. W., Riley, J. L., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.06.015 · Cited by 418 · see citing works
Cellular and Humoral immunity to Different Types of Human Neoplasms
Hellström, I., Hellström, K. E., Pierce, G. E., & Yang, J. P. S. (1968) · Nature · doi:10.1038/2201352a0 · Cited by 394 · see citing works
Kurachi, M., Barnitz, R. A., Yosef, N., Odorizzi, P. M., DiIorio, M. A., Lemieux, M. E., Yates, K. B., Godec, J., Klatt, M. G., Regev, A., et al. (2014) · Nature Immunology · doi:10.1038/ni.2834 · Cited by 384 · see citing works
Zippelius, A., Batard, P., Rubio‐Godoy, V., Bioley, G., Líénard, D., Lejeune, F. J., Rimoldi, D., Guillaume, P., Meidenbauer, N., Mackensen, A., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3066 · Cited by 361 · see citing works
Listeria -based cancer vaccines that segregate immunogenicity from toxicity
Brockstedt, D. G., Giedlin, M. A., Leong, M. L. L., Bahjat, K. S., Gao, Y. Q., Luckett, W. S., Liu, W., Cook, D. N., Portnoy, D. A., & Dubensky, T. W. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406035101 · Cited by 299 · see citing works
Self-citationGeneration of effector CD8 + T cells and their conversion to memory T cells
Cui, W., & Kaech, S. M. (2010) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00926.x · Cited by 287 · see citing works
Endharti, A. T., Rifa, M., Shi, Z., Fukuoka, Y., Nakahara, Y., Kawamoto, Y., Takeda, K., Isobe, K., & Suzuki, H. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.11.7093 · Cited by 271 · see citing works
The Programmed Death-1 Immune-Suppressive Pathway: Barrier to Antitumor Immunity
Ostrand‐Rosenberg, S., Horn, L. A., & Haile, S. T. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1401572 · Cited by 228 · see citing works
Rescued Tolerant CD8 T Cells Are Preprogrammed to Reestablish the Tolerant State
Schietinger, A., Delrow, J. J., Basom, R., Blattman, J. N., & Greenberg, P. D. (2012) · Science · doi:10.1126/science.1214277 · Cited by 172 · see citing works
Self-citationLu, Y., Yao, X., Li, Y. F., El‐Gamil, M., Dudley, M. E., Yang, J. C.-H., Almeida, J. R., Douek, D. C., Samuels, Y., Rosenberg, S. A., et al. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1202830 · Cited by 153 · see citing works
Molecular profiling of CD8 T cells in autochthonous melanoma identifies Maf as driver of exhaustion
Giordano, M., Henin, C., Maurizio, J., Imbratta, C., Bourdely, P., Buferne, M., Baitsch, L., Vanhille, L., Sieweke, M. H., Speiser, D. E., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201490786 · Cited by 129 · see citing works
Orchestrating immune check-point blockade for cancer immunotherapy in combinations
Perez‐Gracia, J. L., Labiano, S., Rodriguez-Ruiz, M. E., Sanmamed, M. F., & Melero, I. (2014) · Current Opinion in Immunology · doi:10.1016/j.coi.2014.01.002 · Cited by 128 · see citing works
Signals from CD28 Induce Stable Epigenetic Modification of the IL-2 Promoter
Thomas, R. M., Gao, L., & Wells, A. D. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.8.4639 · Cited by 122 · see citing works
Specificity in cancer immunotherapy
Schietinger, A., Philip, M., & Schreiber, H. W. (2008) · Seminars in Immunology · doi:10.1016/j.smim.2008.07.001 · Cited by 109 · see citing works
Self-citationAntitumour immunity gets a boost
Wolchok, J. D., & Chan, T. A.-T. (2014) · Nature · doi:10.1038/515496a · Cited by 108 · see citing works
Basic principles of tumor-associated regulatory T cell biology
Savage, P. A., Malchow, S., & Leventhal, D. S. (2012) · Trends in Immunology · doi:10.1016/j.it.2012.08.005 · Cited by 102 · see citing works
Mittrücker, H., Kursar, M., Köhler, A. C., HURWITZ, R. M., & Kaufmann, S. H. E. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.10.5620 · Cited by 89 · see citing works
Staveley-O’Carroll, K. F., Schell, T. D., Jimenez, M., Mylin, L. M., Tevethia, M. J., Schoenberger, S. P., & Tevethia, S. S. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.2.697 · Cited by 79 · see citing works
Self-citationNaturally occurring T-cell response against mutated p21 ras oncoprotein in pancreatic cancer.
Kubuschok, B., Neumann, F., Breit, R., Sester, M., Schormann, C., Wagner, C., Sester, U., Hartmann, F., Wagner, M., REMBERGER, K., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-1672 · Cited by 58 · see citing works
The only proposed T-cell epitope derived from the TEL-AML1 translocation is not naturally processed
Popović, J., Li, L., Kloetzel, P. M., Leisegang, M., Uckert, W., & Blankenstein, T. J. F. (2011) · Blood · doi:10.1182/blood-2010-12-325035 · Cited by 41 · see citing works
Sinnathamby, G., Lauer, P., Zerfass, J., Hanson, B., Karabudak, A., Krakover, J. D., Secord, A. A., Clay, T. M., Morse, M. A., Dubensky, T. W., et al. (2009) · Journal of Immunotherapy · doi:10.1097/cji.0b013e3181b0b125 · Cited by 31 · see citing works
Self-citationStahl, S. H., Sacher, T., Bechtold, A., Protzer, U., Ganß, R., Hämmerling, G. J., Arnold, B., & Garbi, N. (2009) · Immunology Letters · doi:10.1016/j.imlet.2009.01.011 · Cited by 26 · see citing works
Self-citationKhalili, J. S., Hanson, R. W., & Szállási, Z. (2012) · OncoImmunology · doi:10.4161/onci.21511 · Cited by 21 · see citing works
Histologic Characterization of Hepatic Carcinogenesis in Transgenic Mice Expressing SV40 T-antigens
Cullen, J. M., Sandgren, E. P., Brinster, R. L., & Maronpot, R. R. (1993) · Veterinary Pathology · doi:10.1177/030098589303000203 · Cited by 18 · see citing works
Comerford, S. A., Schultz, N. D., Hinnant, E. A., Klapproth, S., & Hammer, R. E. (2012) · Oncogenesis · doi:10.1038/oncsis.2012.27 · Cited by 18 · see citing works
Philip, M., Schietinger, A., & Schreiber, H. W. (2010) · Immunology · doi:10.1111/j.1365-2567.2010.03258.x · Cited by 11 · see citing works
Self-citation
Flagged first, then by citations
1 of the 60 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Understanding the tumor immune microenvironment (TIME) for effective therapy
Binnewies, M., Roberts, E. W., Kersten, K., Chan, V., Fearon, D. F., Merad, M., Coussens, L. M., Gabrilovich, D. I., Ostrand-Rosenberg, S., Hedrick, C. C., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0014-x · Cited by 6,145 · see citing works
Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response
Jiang, P., Gu, S., Pan, D., Fu, J., Sahu, A., Hu, X., Li, Z., Traugh, N., Bu, X., Li, B., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0136-1 · Cited by 5,179 · see citing works
The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy
Havel, J. J., Chowell, D., & Chan, T. A. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0116-x · Cited by 2,286 · 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
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 1,975 · see citing works
Lineage tracking reveals dynamic relationships of T cells in colorectal cancer
Zhang, L., Yu, X., Zheng, L., Zhang, Y., Li, Y., Fang, Q., Gao, R., Kang, B., Zhang, Q., Huang, J. Y., et al. (2018) · Nature · doi:10.1038/s41586-018-0694-x · Cited by 1,505 · 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
Self-citationCD4+ 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 · see citing works
Engineering strategies to overcome the current roadblocks in CAR T cell therapy
Rafiq, S., Hackett, C. S., & Brentjens, R. J. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0297-y · Cited by 1,477 · see citing works
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 1,439 · see citing works
Thommen, D. S., & Schumacher, T. N. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.012 · Cited by 1,304 · see citing works
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 · see citing works
“…was used to determine whether predefined exhaustion gene sets showed enrichment in the PD-1T and PD-1N subsets (Crawford et al., 2014; Schietinger et al., 2016, Gupta et al., 2015, Quigley et al., 2010, Zheng et al., 2017, Doering et al., 2012, Baitsch et al., 2011, Tirosh et al.,…”
MethodInfluentialTOX is a critical regulator of tumour-specific T cell differentiation
Scott, A. C., Dündar, F., Zumbo, P., Chandran, S. S., Klebanoff, C. A., Shakiba, M., Trivedi, P., Menocal, L., Appleby, H., Camara, S., et al. (2019) · Nature · doi:10.1038/s41586-019-1324-y · Cited by 1,106 · see citing works
Self-citationLi, 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 · see citing works
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 1,084 · see citing works
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 · see citing works
Self-citationSun, L., Su, Y., Jiao, A., Wang, X., & Zhang, B. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01471-y · Cited by 1,060 · 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
Self-citationNR4A 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 · see citing works
Contribution of NK cells to immunotherapy mediated by PD-1/PD-L1 blockade
Hsu, J., Hodgins, J. J., Marathe, M., Nicolai, C. J., Bourgeois-Daigneault, M.-C., Trevino, T. N., Azimi, C. S., Scheer, A. K., Randolph, H. E., Thompson, T. W., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci99317 · Cited by 817 · see citing works
Seo, 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 · see citing works
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 815 · see citing works
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 · see citing works
Cold and hot tumors: from molecular mechanisms to targeted therapy
Wu, B., Zhang, B., Li, B., Wu, H., & Jiang, M. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01979-x · Cited by 751 · see citing works
Obstacles Posed by the Tumor Microenvironment to T cell Activity: A Case for Synergistic Therapies
Anderson, K. G., Stromnes, I. M., & Greenberg, P. D. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.02.008 · Cited by 706 · see citing works
Self-citationTargeting 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 653 · see citing works
Unleashing Type-2 Dendritic Cells to Drive Protective Antitumor CD4+ T Cell Immunity
Binnewies, M., Mujal, A. M., Pollack, J. L., Combes, A. J., Hardison, E. A., Barry, K. C., Tsui, J. L., Ruhland, M. K., Kersten, K., Abushawish, M., et al. (2019) · Cell · doi:10.1016/j.cell.2019.02.005 · Cited by 629 · see citing works
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 629 · see citing works
Disturbed mitochondrial dynamics in CD8+ TILs reinforce T cell exhaustion
Yu, Y.-R., Imrichova, H., Wang, H., Chao, T., Xiao, Z., Gao, M., Rincon-Restrepo, M., Franco, F., Genolet, R., Cheng, W.-C., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0793-3 · Cited by 593 · see citing works
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
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 574 · see citing works
Immune checkpoints and their inhibition in cancer and infectious diseases
Dyck, L., & Mills, K. H. G. (2017) · European Journal of Immunology · doi:10.1002/eji.201646875 · Cited by 541 · see citing works
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 548 · see citing works
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 · see citing works
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 501 · see citing works
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 487 · see citing works
Precursor 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 463 · see citing works
Dendritic Cell Paucity Leads to Dysfunctional Immune Surveillance in Pancreatic Cancer
Hegde, S., Lander, V. E., Herzog, B. H., Zuo, C., Breden, M. A., Knolhoff, B. L., Hogg, G. D., Tang, J. P., Baer, J. M., Mpoy, C., et al. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.02.008 · Cited by 454 · see citing works
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 457 · see citing works
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 460 · see citing works
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 473 · see citing works
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 · see citing works
The emerging role of epigenetic therapeutics in immuno-oncology
Topper, M. J., Vaz, M., Marrone, K. A., Brahmer, J. R., & Baylin, S. B. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0266-5 · Cited by 433 · see citing works
Influence of the Tumor Microenvironment on NK Cell Function in Solid Tumors
Melaiu, O., Lucarini, V., Cifaldi, L., & Fruci, D. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2019.03038 · Cited by 418 · see citing works
Ahrends, T., Spanjaard, A., Pilzecker, B., Bąbała, N., Bovens, A. A., Xiao, Y., Jacobs, H., & Borst, J. G. (2017) · Immunity · doi:10.1016/j.immuni.2017.10.009 · Cited by 406 · see citing works
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 403 · see citing works
T Cell Dysfunction and Exhaustion in Cancer
Zhang, Z., Liu, S., Zhang, B., Qiao, L., Zhang, Y., & Zhang, Y. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00017 · Cited by 385 · see citing works
Epigenetic regulation in the tumor microenvironment: molecular mechanisms and therapeutic targets
Yang, J., Xu, J., Wang, W. T., Zhang, B., Yu, X., & Shi, S. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01480-x · Cited by 404 · see citing works
An ex vivo tumor fragment platform to dissect response to PD-1 blockade in cancer
Voabil, P., de Bruijn, M., Roelofsen, L. M., Hendriks, S. H., Brokamp, S., van den Braber, M., Broeks, A., Sanders, J., Herzig, P., Zippelius, A., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01398-3 · Cited by 380 · see citing works
Emerging Cellular Therapies for Cancer
Guedan, S., Ruella, M., & June, C. H. (2018) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042718-041407 · Cited by 386 · see citing works
Cong, J., Wang, X., Zheng, X., Wang, D., Fu, B., Sun, R., Tian, Z., & Wei, H. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.06.021 · Cited by 376 · see citing works
Belk, J. A., Yao, W., Ly, N., Freitas, K. A., Chen, Y.-T., Shi, Q., Valencia, A. M., Shifrut, E., Kale, N., Yost, K. E., et al. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.06.001 · Cited by 382 · see citing works
Prokhnevska, N., Cardenas, M. A., Valanparambil, R. M., Sobierajska, E., Barwick, B. G., Jansen, C. S., Reyes, A. M., Gregorova, P., del Balzo, L., Greenwald, R., et al. (2022) · Immunity · doi:10.1016/j.immuni.2022.12.002 · Cited by 372 · see citing works
Spatiotemporal Co-Dependency between Macrophages and Exhausted CD8 + T Cells in Cancer
Kersten, K., Hu, K. H., Combes, A. J., Samad, B., Harwin, T., Ray, A., Rao, A. A., Cai, E., Marchuk, K., Artichoker, J., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2022.05.004 · Cited by 348 · see citing works
Unraveling the crosstalk between melanoma and immune cells in the tumor microenvironment
Marzagalli, M., Ebelt, N. D., & Manuel, E. R. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.08.002 · Cited by 345 · see citing works
Exhausted CD8+T Cells in the Tumor Immune Microenvironment: New Pathways to Therapy
Jiang, W., He, Y., He, W., Wu, G. S., Zhou, X., Sheng, Q., Zhong, W., Lu, Y., Ding, Y., Qi, L., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.622509 · Cited by 340 · see citing works
T Cell Dysfunction in Cancer Immunity and Immunotherapy
Xia, A., Zhang, Y., Jiang, X., Yin, T., & Lu, X. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01719 · Cited by 338 · see citing works
Two subsets of stem-like CD8+ memory T cell progenitors with distinct fate commitments in humans
Galletti, G., De Simone, G., Mazza, E. M. C., Puccio, S., Mezzanotte, C., Bi, T. M., Davydov, A. N., Metsger, M., Scamardella, E., Alvisi, G., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0791-5 · Cited by 299 · see citing works
Verma, V., Shrimali, R. K., Ahmad, S., Dai, W., Wang, H., Lu, S., Nandre, R., Gaur, P., Lopez, J., Sade-Feldman, M., et al. (2019) · Nature Immunology · doi:10.1038/s41590-019-0441-y · Cited by 333 · see citing works
Epigenetic regulation of T cell exhaustion
Belk, J. A., Dániel, B., & Satpathy, A. T. (2022) · Nature Immunology · doi:10.1038/s41590-022-01224-z · Cited by 334 · see citing works
Exhaustion-associated regulatory regions in CD8 + tumor-infiltrating T cells
Mognol, G. P., Spreafico, R., Wong, V., Scott-Browne, J. P., Togher, S., Hoffmann, A., Hogan, P. G., Rao, A., & Trifari, S. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1620498114 · Cited by 312 · see citing works
Dynamic Changes in Chromatin Accessibility Occur in CD8 + T Cells Responding to Viral Infection
Scott-Browne, J. P., López-Moyado, I. F., Trifari, S., Wong, V., Chávez, L., Rao, A., & Pereira, R. M. (2016) · Immunity · doi:10.1016/j.immuni.2016.10.028 · Cited by 309 · see citing works
Singh, N., Lee, Y. G., Shestova, O., Ravikumar, P., Hayer, K. E., Hong, S. J., Lu, X. M., Pajarillo, R., Agarwal, S., Kuramitsu, S., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0813 · Cited by 295 · see citing works
Reversing T-cell Exhaustion in Cancer: Lessons Learned from PD-1/PD-L1 Immune Checkpoint Blockade
Budimir, N., Thomas, G. D., Dolina, J. S., & Salek‐Ardakani, S. (2021) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-21-0515 · Cited by 302 · see citing works
PD-1/PD-L1 Blockade: Have We Found the Key to Unleash the Antitumor Immune Response?
Xu-Monette, Z. Y., Zhang, M., Li, J., & Young, K. H. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01597 · Cited by 290 · see citing works
Schenkel, J. M., Herbst, R. H., Canner, D. A., Li, A., Hillman, M., Shanahan, S.-L., Gibbons, G., Smith, O. C. G., Kim, J. Y., Westcott, P. M. K., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.08.026 · Cited by 287 · see citing works
Dong, L., Chen, C., Zhang, Y., Guo, P., Wang, Z., Li, J., Liu, Y., Liu, J., Chang, R., Li, Y., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.04.016 · Cited by 280 · see citing works
Philipp, N., Pasikhani, M. K., Nicholls, A., Vick, B., Wulf, J., Straub, T., Scheurer, M., Muth, A., Hänel, G., Nixdorf, D., et al. (2022) · Blood · doi:10.1182/blood.2022015956 · Cited by 285 · see citing works
Freed-Pastor, W. A., Lambert, L. J., Ely, Z. A., Pattada, N. B., Bhutkar, A., Eng, G., Mercer, K. L., Garcia, A. P., Lin, L., Rideout, W. M., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.07.007 · Cited by 273 · see citing works
Cancer immune evasion, immunoediting and intratumour heterogeneity
Roerden, M., & Spranger, S. (2025) · Nature reviews. Immunology · doi:10.1038/s41577-024-01111-8 · Cited by 286 · see citing works
Rethinking peripheral T cell tolerance: checkpoints across a T cell’s journey
ElTanbouly, M. A., & Noelle, R. J. (2020) · Nature reviews. Immunology · doi:10.1038/s41577-020-00454-2 · Cited by 267 · see citing works
Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma
Au, L., Hatipoglu, E., de Massy, M. R., Litchfield, K., Beattie, G., Rowan, A., Schnidrig, D., Thompson, R. H., Byrne, F., Horswell, S. D., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.10.001 · Cited by 258 · see citing works
Challenges in developing personalized neoantigen cancer vaccines
Katsikis, P. D., Ishii, K. J., & Schliehe, C. (2023) · Nature reviews. Immunology · doi:10.1038/s41577-023-00937-y · Cited by 266 · see citing works
Peña-Romero, A. C., & Orenes‐Piñero, E. (2022) · Cancers · doi:10.3390/cancers14071681 · Cited by 262 · see citing works
Collier, J. L., Weiss, S. A., Pauken, K. E., Sen, D. R., & Sharpe, A. H. (2021) · Nature Immunology · doi:10.1038/s41590-021-00949-7 · Cited by 237 · see citing works
Okada, M., Chikuma, S., Kondo, T., Hibino, S., Machiyama, H., Yokosuka, T., Nakano, M., & Yoshimura, A. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.07.027 · Cited by 250 · see citing works
The Contribution of Epigenetics to Cancer Immunotherapy
Villanueva, L., Álvarez‐Errico, D., & Esteller, M. (2020) · Trends in Immunology · doi:10.1016/j.it.2020.06.002 · Cited by 234 · see citing works
Wang, Y., Tong, C., Dai, H., Wu, Z., Han, X., Guo, Y., Chen, D., Wei, J., Ti, D., Liu, Z. Z., et al. (2021) · Nature Communications · doi:10.1038/s41467-020-20696-x · Cited by 237 · see citing works
The yin and yang of co-inhibitory receptors: toward anti-tumor immunity without autoimmunity
Schnell, A., Bod, L., Madi, A., & Kuchroo, V. K. (2020) · Cell Research · doi:10.1038/s41422-020-0277-x · Cited by 225 · see citing works
CRISPR/Cas9-Mediated Knockout of DGK Improves Antitumor Activities of Human T Cells
Jung, I.-Y., Kim, Y.-Y., Yu, H.-S., Lee, M., Kim, S., & Lee, J. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-0030 · Cited by 222 · see citing works
T cell factor 1: A master regulator of the T cell response in disease
Escobar, G., Mangani, D., & Anderson, A. C. (2020) · Science Immunology · doi:10.1126/sciimmunol.abb9726 · Cited by 211 · see citing works
“However, a second study in tumors showed that bulk tumorspecific (Tag-I) CD8+ T cells, harvested early after tumor injection (and likely containing a higher portion of TCF1+ cells), could instead differentiate into functional memory cells when transferred into secondary hosts immunized with Listeria monocytogenes expr…”
BackgroundWilliams, J. B., Horton, B. L., Zheng, Y., Duan, Y., Powell, J. D., & Gajewski, T. F. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20160485 · Cited by 209 · see citing works
T-cell Localization, Activation, and Clonal Expansion in Human Pancreatic Ductal Adenocarcinoma
Stromnes, I. M., Hulbert, A., Pierce, R. H., Greenberg, P. D., & Hingorani, S. R. (2017) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-16-0322 · Cited by 201 · see citing works
Self-citationHuman Anti-tumor Immunity: Insights from Immunotherapy Clinical Trials
Egen, J. G., Ouyang, W., & Wu, L. C. (2020) · Immunity · doi:10.1016/j.immuni.2019.12.010 · Cited by 197 · see citing works
Hou, J., Zhang, H., Sun, B., & Karin, M. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.08.014 · Cited by 191 · see citing works
Chronic stimulation drives human NK cell dysfunction and epigenetic reprograming
Merino, A. M., Zhang, B., Dougherty, P., Luo, X., Wang, J., Blazar, B. R., Miller, J. S., & Cichocki, F. M. (2019) · Journal of Clinical Investigation · doi:10.1172/jci125916 · Cited by 187 · see citing works
Wang, D., Prager, B. C., Gimple, R. C., Aguilar, B., Alizadeh, D., Tang, H., Lv, D., Starr, R., Brito, A., Wu, Q., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1243 · Cited by 185 · see citing works
The function and dysfunction of memory CD 8+ T cells in tumor immunity
Reading, J. L., Gálvez‐Cancino, F., Swanton, C., Lladser, Á., Peggs, K. S., & Quezada, S. A. (2018) · Immunological Reviews · doi:10.1111/imr.12657 · Cited by 182 · see citing works
Low neoantigen expression and poor T-cell priming underlie early immune escape in colorectal cancer
Westcott, P. M. K., Sacks, N. J., Schenkel, J. M., Ely, Z. A., Smith, O. C. G., Hauck, H., Jaeger, A. M., Zhang, D., Backlund, C. M., Beytagh, M. C., et al. (2021) · Nature Cancer · doi:10.1038/s43018-021-00247-z · Cited by 180 · see citing works
Mechanisms of resistance to chimeric antigen receptor-T cells in haematological malignancies
Ruella, M., Korell, F., Porazzi, P., & Maus, M. V. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-023-00807-1 · Cited by 182 · see citing works
Dormant tumour cells, their niches and the influence of immunity
Goddard, E. T., Božić, I., Riddell, S. R., & Ghajar, C. M. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0214-0 · Cited by 176 · 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
Self-citationPolania, J. W., Hoyt-Miggelbrink, A. M., Tomaszewski, W. H., Wachsmuth, L. P., Lorrey, S., Wilkinson, D. S., Lerner, E., Woroniecka, K. I., Finlay, J. B., Ayasoufi, K., et al. (2024) · Immunity · doi:10.1016/j.immuni.2024.11.026 · Cited by 174 · see citing works
Gene modification strategies for next-generation CAR T cells against solid cancers
Tian, Y., Li, Y., Shao, Y., & Zhang, Y. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00890-6 · Cited by 177 · see citing works
Allogeneic CAR-T Cells: More than Ease of Access?
Graham, C., Jóźwik, A., Pepper, A. G. S., & Benjamin, R. (2018) · Cells · doi:10.3390/cells7100155 · Cited by 172 · see citing works
Wang, B., Zhang, W., Jankovic, V., Golubov, J., Poon, P., Oswald, E. M., Gurer, C., Wei, J., Ramos, I., Wu, Q., et al. (2018) · Science Immunology · doi:10.1126/sciimmunol.aat7061 · Cited by 167 · see citing works
Chafe, S. C., McDonald, P. C., Saberi, S., Nemirovsky, O., Venkateswaran, G., Burugu, S., Gao, D., Delaidelli, A., Kyle, A. H., Baker, J. H. E., et al. (2019) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-18-0657 · Cited by 166 · see citing works
CD8+ T cell exhaustion and cancer immunotherapy
Wang, Q., Qin, Y., & Li, B. (2023) · Cancer Letters · doi:10.1016/j.canlet.2022.216043 · Cited by 155 · see citing works
Mechanisms of T-Cell Exhaustion in Pancreatic Cancer
Saka, D., Gökalp, M., Piyade, B., Çevik, N. C., Sever, E. A., Unutmaz, D., Ceyhan, G. O., Demir, İ. E., & Asimgil, H. (2020) · Cancers · doi:10.3390/cancers12082274 · Cited by 154 · see citing works
Bystander T cells in cancer immunology and therapy
Meier, S. L., Satpathy, A. T., & Wells, D. K. (2022) · Nature Cancer · doi:10.1038/s43018-022-00335-8 · Cited by 157 · see citing works
- Authors
- Schietinger, A., Philip, M., Krisnawan, V. E., Chiu, E. Y., Delrow, J. J., Basom, R. S., Lauer, P., Brockstedt, D. G., Knoblaugh, S. E., Hämmerling, G. J., Schell, T. D., Garbi, N., & Greenberg, P. D.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- University of Washington (US)
- Fred Hutch Cancer Center (US)
- Aduro BioTech (United States) (US)
- German Cancer Research Center (DE)
- Pennsylvania State University (US)
- University of Bonn (DE)
- Corresponding author
- Schietinger, Andrea
- Greenberg, Philip D.
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 45
- Issue
- 2
- Pages
- 389-401
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC5119632
- OpenAlex
- W2514996992
- Cited by
- 720
- References
- 60
- Citations by year
- 2026: 45 · 2025: 77 · 2024: 93 · 2023: 84 · 2022: 78 · 2021: 103 · 2020: 99 · 2019: 61 · 2018: 50 · 2017: 25 · 2016: 5
- FWCI
- 25.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R00CA172371, K99CA172371, K08CA158069, R01CA033084, P30CA008748, P30CA015704)
- National Institute of Allergy and Infectious Diseases (R21AI107776)
- 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
- tumor-specific T cells, CD8+ T cell dysfunction, carcinogenesis, SV40 large T antigen, liver cancer, T cell differentiation, T cell exhaustion, cancer immunotherapy
- MeSH terms
- Animals, Antigens, Polyomavirus Transforming, Cell Differentiation, Cells, Cultured, Disease Models, Animal, Humans, Liver Neoplasms, Lymphocyte Activation, Mice, Inbred C57BL, Mice, Transgenic, Tamoxifen, Immunotherapy, Adoptive, Cellular Senescence, CD8-Positive T-Lymphocytes, Cancer Vaccines, Mice, Tumor Microenvironment, Carcinogenesis
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 ›
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