Tumor-induced senescent T cells with suppressor function: a potential form of tumor immune evasion
Open accessAbstract
Senescent and suppressor T cells are reported to be increased in select patients with cancer and are poor prognostic indicators. Based on the association of these T cells and poor outcomes, we hypothesized that tumors induce senescence in T cells, which negatively effects antitumor immunity. In this report, we show that human T cells from healthy donors incubated with tumor for only 6 h at a low tumor to T-cell ratio undergo a senescence-like phenotype, characterized by the loss of CD27 and CD28 expression and telomere shortening. Tumor-induced senescence of T cells is induced by soluble factors and triggers increases in expression of senescence-associated molecules such as p53, p21, and p16. Importantly, these T cells are not only phenotypically altered, but also functionally altered as they can suppress the proliferation of responder T cells. This suppression requires cell-to-cell contact and is mediated by senescent CD4+ and CD8+ subpopulations, which are distinct from classically described natural T regulatory cells. Our observations support the novel concept that tumor can induce senescent T cells with suppressor function and may effect both the diagnosis and treatment of cancer. [Cancer Res 2008;68(3):870–9]
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Tumor cells can induce T cell senescence in in vitro co-cultures.
“In line with this notion, tumor cells can induce T cell senescence in in vitro co-cultures [56].”
From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [56]
Senescent CD8+ T lymphocytes aid tumor immune evasion by being functionally unresponsive and by suppressing responder T cells.
“Senescent CD8 + T lymphocytes not only contribute to tumor immune evasion through their functional unresponsiveness (42) and their suppressor function toward responder T cells (41,43)”
From p53 isoforms regulate aging- and tumor-associated replicative senescence in T lymphocytes (2013) · cites this paper as [41]
Soluble factors from tumors mediate senescence of T lymphocytes.
“Tumor-induced senescence of T lymphocytes is also mediated by tumor-derived soluble factors (41).”
From p53 isoforms regulate aging- and tumor-associated replicative senescence in T lymphocytes (2013) · cites this paper as [41]
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Cites
Cancer regression in patients after transfer of genetically engineered lymphocytes
Morgan, R. A., Dudley, M. E., Wunderlich, J. R., Hughes, M. S., Yang, J. C., Sherry, R. M., Royal, R. E., Topalian, S. L., Kammula, U. S., Restifo, N. P., et al. (2006) · Science · doi:10.1126/science.1129003 · Cited by 2,603 · see citing works
Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors
Campisi, J. (2005) · Cell · doi:10.1016/j.cell.2005.02.003 · Cited by 2,359 · see citing works
Effector Memory T Cells, Early Metastasis, and Survival in Colorectal Cancer
Pagès, F., Berger, A., Camus, M., Sanchez-Cabo, F., Costes, A., Molidor, R., Mlecnik, B., Kirilovsky, A., Nilsson, M., Damotte, D., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa051424 · Cited by 2,135 · cited 1× · see citing works
“poor prognostic indicator in the tumor microenvironment, the opposite has been shown (33, 34).”
BackgroundRegulatory T cells, tumour immunity and immunotherapy
Zou, W. (2006) · Nature reviews. Immunology · doi:10.1038/nri1806 · Cited by 2,075 · see citing works
Phenotypic and functional separation of memory and effector human CD8+ T cells
Hamann, D., Baars, P. A., Rep, M. H. G., Hooibrink, B., Kerkhof-Garde, S. R., Klein, M. R., & Lier, R. A. W. V. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.186.9.1407 · Cited by 1,366 · see citing works
Cellular Senescence in Aging Primates
Herbig, U., Ferreira, M., Condel, L., Carey, D., & Sedivy, J. M. (2006) · Science · doi:10.1126/science.1122446 · Cited by 1,101 · see citing works
Mechanisms of suppression by suppressor T cells
von Boehmer, H. (2005) · Nature Immunology · doi:10.1038/ni1180 · Cited by 1,005 · see citing works
Ghiringhelli, F., Puig, P. E., Roux, S., Parcellier, A., Schmitt, E., Solary, É., Kroemer, G., Martin, F., Chauffert, B., & Zitvogel, L. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050463 · Cited by 776 · see citing works
If not apoptosis, then what? Treatment-induced senescence and mitotic catastrophe in tumor cells
Roninson, I. B., Broude, E. V., & Chang, B.-D. (2001) · Drug Resistance Updates · doi:10.1054/drup.2001.0213 · Cited by 720 · see citing works
Caspases in cell survival, proliferation and differentiation
Lamkanfi, M., Festjens, N., Declercq, W., Berghe, T. V., & Vandenabeele, P. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402047 · Cited by 564 · see citing works
Telomere length dynamics in human lymphocyte subpopulations measured by flow cytometry
Rufer, N., Dragowska, W. H., Thornbury, G., Roosnek, E. E., & Lansdorp, P. M. (1998) · Nature Biotechnology · doi:10.1038/nbt0898-743 · Cited by 547 · see citing works
Liu, V. C., Wong, L. Y., Jang, T. L., Shah, A. H., Park, I. I., Yang, X. J., Zhang, Q., Lonning, S. M., Teicher, B. A., & Lee, C. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.5.2883 · Cited by 453 · see citing works
CD28 extinction in human T cells: altered functions and the program of T‐cell senescence
Vallejo, A. N. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00256.x · Cited by 435 · see citing works
Eom, Y. W., Kim, M. A., Park, S. S., Goo, M. J., Kwon, H. J., Sohn, S., Kim, W., Yoon, G., & Choi, K. S. (2005) · Oncogene · doi:10.1038/sj.onc.1208627 · Cited by 351 · see citing works
Zhou, J., Shen, X., Huang, J., Hodes, R. J., Rosenberg, S. A., & Robbins, P. F. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.10.7046 · Cited by 336 · see citing works
The role of CD8<sup>+</sup> T‐cell replicative senescence in human aging
Effros, R. B., Dagarag, M., Spaulding, C., & Man, J. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00259.x · Cited by 336 · see citing works
Short Telomeres, even in the Presence of Telomerase, Limit Tissue Renewal Capacity
Hao, L.-Y., Armanios, M., Strong, M. A., Karim, B., Feldser, D. M., Huso, D., & Greider, C. W. (2005) · Cell · doi:10.1016/j.cell.2005.11.020 · Cited by 302 · see citing works
Powell, D. J., Dudley, M. E., Robbins, P. F., & Rosenberg, S. A. (2004) · Blood · doi:10.1182/blood-2004-06-2482 · Cited by 291 · see citing works
Down-Regulation of CD28 Expression by TNF-α
Bryl, E., Vallejo, A. N., Weyand, C. M., & Goronzy, J. J. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.6.3231 · Cited by 264 · see citing works
Tarazona, R., DelaRosa, O., Alonso, C., Ostos, B., Espejo, J., Peña, J., & Solana, R. (2001) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(00)00199-8 · Cited by 262 · see citing works
Spaulding, C., Guo, W., & Effros, R. B. (1999) · Experimental Gerontology · doi:10.1016/s0531-5565(99)00033-9 · Cited by 258 · see citing works
Valenzuela, H. (2002) · Clinical Immunology · doi:10.1006/clim.2002.5271 · Cited by 254 · see citing works
Rabinowich, H., Reichert, T. E., Kashii, Y., Gastman, B., Bell, M. C., & Whiteside, T. L. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1518 · Cited by 235 · see citing works
Self-citationFilaci, G., Fenoglio, D., Fravega, M., Ansaldo, G., Borgonovo, G., Traverso, P., Villaggio, B., Ferrera, A., Kunkl, A., Rizzi, M., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.7.4323 · Cited by 229 · see citing works
Aggarwal, S., & Gupta, S. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.4.1627 · Cited by 229 · see citing works
Gastman, B., Atarshi, Y., Reichert, T. E., Saito, T., Balkir, L., Rabinowich, H., & Whiteside, T. L. (1999) · PubMed · Cited by 216 · see citing works
Self-citationMeloni, F., Morosini, M., Solari, N., Passadore, I., Nascimbene, C., Novo, M., Ferrari, M., Cosentino, M., Marino, F., Pozzi, E., et al. (2006) · Human Immunology · doi:10.1016/j.humimm.2005.11.005 · Cited by 169 · see citing works
Impairment of CD8+ T Suppressor Cell Function in Patients with Active Systemic Lupus Erythematosus
Filaci, G., Bacilieri, S., Fravega, M., Monetti, M., Contini, P., Ghio, M., Setti, M., Puppo, F., & Indiveri, F. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.10.6452 · Cited by 165 · see citing works
Filaci, G., Fravega, M., Negrini, S., Procopio, F., Fenoglio, D., Rizzi, M., Brenci, S., Contini, P., Olive, D., Ghio, M., et al. (2004) · Human Immunology · doi:10.1016/j.humimm.2003.12.001 · Cited by 163 · see citing works
Tsukishiro, T., Donnenberg, A. D., & Whiteside, T. L. (2003) · Cancer Immunology, Immunotherapy · doi:10.1007/s00262-003-0395-6 · Cited by 158 · see citing works
Palmer, L. D., Weng, N.-P., Levine, B. L., June, C. H., Lane, H. C., & Hodes, R. J. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.7.1381 · Cited by 129 · see citing works
Renal cell carcinoma–derived gangliosides suppress nuclear factor-κB activation in T cells
Uzzo, R. G., Rayman, P. A., Kolenko, V. M., Clark, P. E., Cathcart, M. K., Bloom, T., Novick, A. C., Bukowski, R. M., Hamilton, T. A., & Finke, J. H. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6775 · Cited by 123 · see citing works
Okada, K., Komuta, K., Hashimoto, S., Matsuzaki, S., Kanematsu, T., & Koji, T. (2000) · PubMed · Cited by 100 · see citing works
Tumor-induced apoptosis of T lymphocytes: elucidation of intracellular apoptotic events
Gastman, B., Johnson, D. E., Whiteside, T. L., & Rabinowich, H. (2000) · Blood · doi:10.1182/blood.v95.6.2015 · Cited by 91 · see citing works
Self-citationExploiting different ways to die: Figure 1.Preprint
Nelson, D. A., & White, E. (2004) · Genes & Development · doi:10.1101/gad.1212404 · Cited by 88 · see citing works
Vallejo, A. N. (2007) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2007.01.005 · Cited by 83 · see citing works
Regulatory T cells and tumor immunity
Chattopadhyay, S., Chakraborty, N. G., & Mukherji, B. (2005) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-005-0699-9 · Cited by 83 · see citing works
Decreased perforin and granzyme B expression in senescent HIV-1-specific cytotoxic T lymphocytes
Yang, O. O., Lin, H., Dagarag, M., Ng, H. L., Effros, R. B., & Uittenbogaart, C. H. (2005) · Virology · doi:10.1016/j.virol.2004.11.028 · Cited by 79 · see citing works
Clonal populations of CD4+ and CD8+ T cells in patients with multiple myeloma and paraproteinemia
Moss, P. A. H., Gillespie, G. M. A., Frodsham, P., Bell, J., & Reyburn, H. T. (1996) · Blood · doi:10.1182/blood.v87.8.3297.bloodjournal8783297 · Cited by 79 · see citing works
Kuss, I., Donnenberg, A. D., Gooding, W. E., & Whiteside, T. L. (2003) · British Journal of Cancer · doi:10.1038/sj.bjc.6600694 · Cited by 73 · see citing works
Resistance to Granzyme B-mediated Cytochrome c Release in Bak-deficient Cells
Wang, G.-Q., Wieckowski, E. U., Goldstein, L. A., Gastman, B., Rabinovitz, A., Gambotto, A. A., Li, S., Fang, B., Yin, X., & Rabinowich, H. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.9.1325 · Cited by 71 · see citing works
Self-citationTanaka, T., Kajstura, M. A., Halicka, H. D., Traganos, F., & Darżynkiewicz, Z. (2007) · Cell Proliferation · doi:10.1111/j.1365-2184.2007.00417.x · Cited by 63 · see citing works
Frydecka, I., Kosmaczewska, A., Boćko, D., Ciszak, L., Wołowiec, D., Kuliczkowski, K., & Kochanowska, I. E. (2004) · British Journal of Cancer · doi:10.1038/sj.bjc.6601833 · Cited by 56 · see citing works
Prado-Garcı́a, H., Aguilar‐Cázares, D., Flores-Vergara, H., Mandoki, J. J., & López-González, J. S. (2004) · Lung Cancer · doi:10.1016/j.lungcan.2004.07.046 · Cited by 51 · see citing works
Sindhi, R. K., Manavalan, J. S., Magill, A., Suciu‐Foca, N., & Zeevi, A. (2005) · Human Immunology · doi:10.1016/j.humimm.2004.05.017 · Cited by 35 · see citing works
Mechanisms That Limit the In Vitro Proliferative Potential of Human CD8+ T Lymphocytes
Migliaccio, M., Raj, K., Menzel, O., & Rufer, N. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.6.3335 · Cited by 29 · see citing works
Maki, A., Matsuda, M., Asakawa, M., Kono, H., Fujii, H., & Matsumoto, Y. (2004) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2004.03455.x · Cited by 25 · see citing works
Pilch, H., Hoehn, H., Schmidt, M., Steiner, E. A., Tanner, B., Seufert, R., & Maeurer, M. J. (2002) · Zentralblatt für Gynäkologie · doi:10.1055/s-2002-38130 · Cited by 18 · see citing works
Martínez‐Escribano, J., Hernández‐Caselles, T., Campillo, J. A., Campos, M., Frías, J. F., García-Alonso, A. M., & Álvarez-López, M. R. (2003) · Human Immunology · doi:10.1016/s0198-8859(03)00122-8 · Cited by 16 · see citing works
Biochemotherapy of metastatic malignant melanoma. On down-regulation of CD28
Håkansson, A., Håkansson, L., Gustafsson, B., Krysander, L., Rettrup, B., Ruiter, D. J., & Bernsen, M. R. (2002) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-002-0304-4 · Cited by 16 · see citing works
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- Nelson DA, White E. Exploiting different ways to die. Genes Dev 2004;18:1223-6.
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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
Inflammation and cancer: interweaving microRNA, free radical, cytokine and p53 pathways
Schetter, A. J., Heegaard, N. H. H., & Harris, C. C. (2009) · Carcinogenesis · doi:10.1093/carcin/bgp272 · Cited by 659 · see citing works
Ganesan, A.-P., Clarke, J., Wood, O., Garrido-Martin, E. M., Chee, S. J., Mellows, T., Samaniego-Castruita, D., Singh, D., Seumois, G., Alzetani, A., et al. (2017) · Nature Immunology · doi:10.1038/ni.3775 · Cited by 528 · see citing works
Exhaustion and senescence: two crucial dysfunctional states of T cells in the tumor microenvironment
Zhao, Y., Shao, Q., & Peng, G. (2020) · Cellular & Molecular Immunology · doi:10.1038/s41423-019-0344-8 · Cited by 382 · see citing works
T Cell Replicative Senescence in Human Aging
P. Chou, J., & B. Effros, R. (2013) · Current Pharmaceutical Design · doi:10.2174/138161213805219711 · Cited by 323 · see citing works
Effector, Memory, and Dysfunctional CD8+T Cell Fates in the Antitumor Immune Response
Reiser, J., & Banerjee, A. (2016) · Journal of Immunology Research · doi:10.1155/2016/8941260 · Cited by 256 · see citing works
Causes of genome instability: the effect of low dose chemical exposures in modern society
Langie, S. A. S., Koppen, G., Desaulniers, D. M., Al‐Mulla, F., Al-Temaimi, R. A., Amedei, A., Azqueta, A., Bisson, W. H., Brown, D. G., Brunborg, G., et al. (2015) · Carcinogenesis · doi:10.1093/carcin/bgv031 · Cited by 229 · see citing works
Two-Step Senescence-Focused Cancer Therapies
Sieben, C. J., Sturmlechner, I., van de Sluis, B., & van Deursen, J. M. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.04.006 · Cited by 222 · see citing works
Cellular senescence: Immunosurveillance and future immunotherapy
Burton, D. G. A., & Stolzing, A. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.02.001 · Cited by 221 · see citing works
Ye, J., Ma, C., Hsueh, E. C., Eickhoff, C. S., Zhang, Y., Varvares, M. A., Hoft, D. F., & Peng, G. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1202369 · Cited by 203 · see citing works
Human regulatory T cells induce T-lymphocyte senescence
Ye, J., Huang, X., Hsueh, E. C., Zhang, Q., Ma, C., Zhang, Y., Varvares, M. A., Hoft, D. F., & Peng, G. (2012) · Blood · doi:10.1182/blood-2012-03-416040 · Cited by 198 · see citing works
Tumor-derived exosomes induce CD8+ T cell suppressors
Maybruck, B. T., Pfannenstiel, L. W., Díaz-Montero, M., & Gastman, B. (2017) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-017-0269-7 · Cited by 194 · see citing works
Self-citationSenescent T cells: a potential biomarker and target for cancer therapy
Zhang, J., He, T., Xue, L., & Guo, H. (2021) · EBioMedicine · doi:10.1016/j.ebiom.2021.103409 · Cited by 171 · see citing works
p53 isoforms regulate aging- and tumor-associated replicative senescence in T lymphocytes
Mondal, A. M., Horikawa, I., Pine, S. R., Fujita, K., Morgan, K. M., Vera, E., Mazur, S. J., Appella, E., Vojtesek, B., Blasco, M. A., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci70355 · Cited by 164 · see citing works
Tumor‐Derived Exosomes in Immunosuppression and Immunotherapy
Olejarz, W., Dominiak, A., Żołnierzak, A., Kubiak-Tomaszewska, G., & Lorenc, T. (2020) · Journal of Immunology Research · doi:10.1155/2020/6272498 · Cited by 164 · see citing works
TLR8 signaling enhances tumor immunity by preventing tumor‐induced T‐cell senescence
Ye, J., Ma, C., Hsueh, E. C., Dou, J., Mo, W., Liu, S., Han, B., Huang, Y., Zhang, Y., Varvares, M. A., et al. (2014) · EMBO Molecular Medicine · doi:10.15252/emmm.201403918 · Cited by 161 · see citing works
Cellular senescence impact on immune cell fate and function
Vicente, R., Mausset-Bonnefont, A.-L., Jorgensen, C., Louis-Plence, P., & Brondello, J.-M. (2016) · Aging Cell · doi:10.1111/acel.12455 · Cited by 151 · see citing works
Exhaustion of T lymphocytes in the tumor microenvironment: Significance and effective mechanisms
Gholami, M. D., Kardar, G. A., Saeedi, Y., Heidari, S., Garssen, J., & Falak, R. (2017) · Cellular Immunology · doi:10.1016/j.cellimm.2017.10.002 · Cited by 140 · see citing works
Consensus nomenclature for CD8+T cell phenotypes in cancer
Apétoh, L., Smyth, M. J., Drake, C. G., Abastado, J., Apte, R. N., Ayyoub, M., Blay, J., Bonneville, M., Butterfield, L. H., Caignard, A., et al. (2015) · OncoImmunology · doi:10.1080/2162402x.2014.998538 · Cited by 138 · see citing works
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HCC-Derived Exosomes: Critical Player and Target for Cancer Immune Escape
Han, Q., Zhao, H., Yu, J., Yin, C., & Zhang, J. (2019) · Cells · doi:10.3390/cells8060558 · Cited by 119 · see citing works
Liu, X., Hoft, D. F., & Peng, G. (2020) · Journal of Clinical Investigation · doi:10.1172/jci133679 · Cited by 113 · see citing works
Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in head and neck cancers.
Uppaluri, R., Dunn, G. P., & Lewis, J. S. (2008) · PubMed Central · Cited by 109 · see citing works
Liu, X., Si, F., Bagley, D., Ma, F., Zhang, Y., Tao, Y., Shaw, E. C., & Peng, G. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2022-005020 · Cited by 100 · see citing works
Rutella, S., Vadakekolathu, J. N., Mazziotta, F., Reeder, S., Yau, T. O., Mukhopadhyay, R., Dickins, B., Altmann, H., Krämer, M., Knaus, H. A., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci159579 · Cited by 95 · see citing works
A high OXPHOS CD8 T cell subset is predictive of immunotherapy resistance in melanoma patients
Li, C., Phoon, Y. P., Karlinsey, K. S., Tian, Y. F., Thapaliya, S., Thongkum, A., Qu, L., Matz, A., Cameron, M. J., Cameron, C., et al. (2021) · The Journal of Experimental Medicine · doi:10.1084/jem.20202084 · Cited by 86 · see citing works
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Carroll, R. P., Segundo, D. S., Hollowood, K., Marafioti, T., Clark, T. G., Harden, P., & Wood, K. J. (2010) · Journal of the American Society of Nephrology · doi:10.1681/asn.2009060669 · Cited by 89 · see citing works
Tumor-derived ILT4 induces T cell senescence and suppresses tumor immunity
Gao, A., Liu, X., Lin, W., Wang, J., Wang, S., Si, F., Huang, L. J., Zhao, Y., Sun, Y., & Peng, G. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-001536 · Cited by 87 · see citing works
Bigley, A. B., Spielmann, G., LaVoy, E. C. P., & Simpson, R. J. (2013) · Maturitas · doi:10.1016/j.maturitas.2013.06.010 · Cited by 75 · see citing works
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Zingoni, A., Antonangeli, F., Sozzani, S., Santoni, A., Cippitelli, M., & Soriani, A. (2024) · Molecular Cancer · doi:10.1186/s12943-024-01973-5 · Cited by 74 · see citing works
Golomb, L., Sagiv, A., Pateras, I. S., Maly, A., Krizhanovsky, V, Gorgoulis, V. G., Oren, M., & Ben-Yehuda, A. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2015.21 · Cited by 71 · see citing works
Zou, Q., Wang, X.-L., Ren, D., Hu, B., Tang, G.-N., Zhang, Y., Huang, M.-J., Pai, R., Buchanan, D., Win, A., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-002671 · Cited by 60 · see citing works
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Senescence in the Development and Response to Cancer with Immunotherapy: A Double-Edged Sword
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The clinical implications of antitumor immunity in head and neck cancer
Allen, C. T., Judd, N. P., Bui, J. D., & Uppaluri, R. (2011) · The Laryngoscope · doi:10.1002/lary.21913 · Cited by 59 · see citing works
Knowns and Unknowns about CAR-T Cell Dysfunction
Titov, A., Kaminskiy, Y., Ganeeva, I., Zmievskaya, E., Valiullina, A., Rakhmatullina, A., Petukhov, A., Рифкатовна, М. Р., Rizvanov, A. A., & Bulatov, E. (2022) · Cancers · doi:10.3390/cancers14041078 · Cited by 56 · see citing works
Dai, D., Pei, Y., Zhu, B., Wang, D., Pei, S., Huang, H., Zhu, Q., Deng, X., Ye, J., Xu, J., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101550 · Cited by 53 · see citing works
Immune-Checkpoint Blockade Opposes CD8+ T-cell Suppression in Human and Murine Cancer
Pfannenstiel, L. W., Diaz-Montero, C. M., Tian, Y. F., Scharpf, J., Ko, J. S., & Gastman, B. (2019) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-18-0054 · Cited by 49 · see citing works
Self-citationRamello, M. C., Tosello, J., Canale, F. P., Mena, H. A., Negrotto, S., Gastman, B., Gruppi, A., Rodríguez, E. V. A., & Montes, C. L. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.451 · Cited by 49 · see citing works
Self-citationCellular Senescence and Periodontitis: Mechanisms and Therapeutics
Chen, S., Zhou, D., Liu, O., Chen, H., Wang, Y., & Zhou, Y. (2022) · Biology · doi:10.3390/biology11101419 · Cited by 49 · see citing works
Janelle, V., & Delisle, J. (2021) · Cancers · doi:10.3390/cancers13040598 · Cited by 51 · see citing works
Disruptive environmental chemicals and cellular mechanisms that confer resistance to cell death
Narayanan, K. B., Ali, M., Barclay, B. J., Cheng, Q. S., D'Abronzo, L. S., Dornetshuber-Fleiss, R., Ghosh, P., Guzman, M. J. G., Lee, T. J., Leung, P. S., et al. (2015) · Carcinogenesis · doi:10.1093/carcin/bgv032 · Cited by 47 · see citing works
The P2X7 Receptor in Tumor Immunity
Grassi, F., & Conti, B. D. P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.694831 · Cited by 42 · see citing works
Ramello, M. C., Núñez, N. G., Tosello, J., Bossio, S., Canale, F. P., Abrate, C., Ponce, N. E., del Castillo, A., Ledesma, M., Viel, S., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.713132 · Cited by 45 · see citing works
Self-citationSenescence and Immunoregulation in the Tumor Microenvironment
Ruhland, M. K., & Alspach, E. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.754069 · Cited by 43 · see citing works
Mkhobongo, B., Chandran, R., & Abrahamse, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22189726 · Cited by 42 · see citing works
Gao, Q., Zhou, J., Wang, X., Qiu, S., Song, K., Huang, X., Sun, J., Shi, Y., Li, B., Xiao, Y., et al. (2011) · Annals of Surgical Oncology · doi:10.1245/s10434-011-1864-3 · Cited by 41 · see citing works
The Different Functional Distribution of “Not Effector” T Cells (Treg/Tnull) in Colorectal Cancer
Niccolai, E., Ricci, F., Russo, E., Nannini, G., Emmi, G., Taddei, A., Ringressi, M. N., Melli, F., Miloeva, M., Cianchi, F., et al. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01900 · Cited by 40 · see citing works
Senescence of Tumor Cells in Anticancer Therapy—Beneficial and Detrimental Effects
Piskorz, W. M., & Cechowska‐Pasko, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911082 · Cited by 39 · see citing works
Parmar, H. V., Gertz, M. A., Anderson, E. I., Kumar, S. K., & Kourelis, T. (2021) · Blood Advances · doi:10.1182/bloodadvances.2020003857 · Cited by 38 · see citing works
T-cell Exhaustion in Organ Transplantation
Angeletti, A., Cantarelli, C., Riella, L. V., Fribourg, M., & Cravedi, P. (2021) · Transplantation · doi:10.1097/tp.0000000000003851 · Cited by 38 · see citing works
T cell senescence: a new perspective on immunotherapy in lung cancer
Huang, M., Wang, Y., Fang, L., Liu, C., Feng, F., Liu, L., & Sun, C. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1338680 · Cited by 37 · see citing works
Extracellular Vesicles and Cancer Stem Cells in Tumor Progression: New Therapeutic Perspectives
Scioli, M. G., Terriaca, S., Fiorelli, E., Storti, G., Fabbri, G., Cervelli, V., & Orlandi, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910572 · Cited by 37 · see citing works
Theranostic signature of tumor-derived exosomes in cancer
Kumar, S., Dhar, R., Kumar, L., Shivji, G. G., Jayaraj, R., & Devi, A. (2023) · Medical Oncology · doi:10.1007/s12032-023-02176-6 · Cited by 29 · see citing works
Zhang, Y., Pfannenstiel, L. W., Bolesta, E., Montes, C. L., Zhang, X., Chapoval, A. I., Gartenhaus, R. B., Strome, S. E., & Gastman, B. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-3328 · Cited by 35 · see citing works
Self-citationKhan, F. H., Reza, M. J., Shao, Y. F., Perwez, A., Zahra, H., Dowlati, A., & Abbas, A. (2022) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2022.188776 · Cited by 34 · see citing works
Biomechanics of T Cell Dysfunctions in Chronic Diseases
Gunasinghe, S. D., Peres, N. G., Goyette, J., & Gaus, K. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.600829 · Cited by 31 · see citing works
Cigarette smoking induces human CCR6+Th17 lymphocytes senescence and VEGF-A secretion
Baskara, I., Kerbrat, S., Dagouassat, M., Nguyen, H. Q., Guillot‐Delost, M., Surénaud, M., Baillou, C., Lemoine, F. M., Morin, D., Boczkowski, J., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-63613-4 · Cited by 32 · see citing works
Wang, H., Yu, Y., Li, R., Zhang, H., Chen, Z., Sun, C., & Zhuang, J. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.07.022 · Cited by 32 · see citing works
Weng, J., Moriarty, K. E., Baio, F. E., Chu, F., Kim, S.-D., He, J., Jie, Z., Xie, X., Ma, W., Qian, J., et al. (2016) · OncoImmunology · doi:10.1080/2162402x.2016.1237327 · Cited by 28 · see citing works
Huff, W. X., Bam, M., Shireman, J. M., Kwon, J. H., Song, L., Newman, S., Cohen‐Gadol, A., Shapiro, S., Jones, T., Fulton, K., et al. (2021) · ImmunoHorizons · doi:10.4049/immunohorizons.2100008 · Cited by 28 · see citing works
A Critical Appraisal of the Utility of Targeting Therapy-Induced Senescence for Cancer Treatment
Saleh, T., Greenberg, E. F., Faber, A. C., Harada, H., & Gewirtz, D. A. (2025) · Cancer Research · doi:10.1158/0008-5472.can-24-2219 · Cited by 26 · see citing works
Senescent Stromal Cells in the Tumor Microenvironment: Victims or Accomplices?
Ye, M., Huang, X., Wu, Q., & Liu, F. (2023) · Cancers · doi:10.3390/cancers15071927 · Cited by 26 · see citing works
T cell exhaustion and senescence for ovarian cancer immunotherapy
Zhao, J., Wang, Z., Tian, Y., Ning, J., & Ye, H. (2024) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2024.07.001 · Cited by 25 · see citing works
Senescent Tumor CD8+ T Cells: Mechanisms of Induction and Challenges to Immunotherapy
Liu, W., Stachura, P., Xu, H. C., Bhatia, S., Borkhardt, A., Lang, P. A., & Pandyra, A. A. (2020) · Cancers · doi:10.3390/cancers12102828 · Cited by 24 · see citing works
Liu, Y., Hawkins, O. E., Vilgelm, A. E., Pawlikowski, J. S., Ecsedy, J., Sosman, J. A., Kelley, M. C., & Richmond, A. J. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0293 · Cited by 25 · see citing works
Landon‐Brace, N., Li, N. T., & McGuigan, A. P. (2023) · Advanced Healthcare Materials · doi:10.1002/adhm.202300903 · Cited by 24 · see citing works
Thoma, O., Naschberger, E., Kubánková, M., Larafa, I., Kramer, V., Menchicchi, B., Merkel, S., Britzen‐Laurent, N., Jefremow, A., Grützmann, R., et al. (2023) · Gastroenterology · doi:10.1053/j.gastro.2023.09.017 · Cited by 22 · see citing works
Yan, Y., Lu, J., Luo, H., Wang, Z., Xu, K., Wang, L., & Wang, Q. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1667464 · Cited by 23 · see citing works
Mitchell, M., & Loudig, O. (2023) · Biomedicines · doi:10.3390/biomedicines11092534 · Cited by 23 · see citing works
Cellular senescence in tumor immune escape: Mechanisms, implications, and therapeutic potential
Li, Y., & Wu, Q. (2025) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2025.104628 · Cited by 19 · see citing works
Implications of Senescent T Cells for Cancer Immunotherapy
Kasamatsu, T. (2023) · Cancers · doi:10.3390/cancers15245835 · Cited by 20 · see citing works
Shorter telomere length of T-cells in peripheral blood of patients with lung cancer
Yang, L., Qian, Y., Ding, T., Wei, L., & Cao, S. (2016) · OncoTargets and Therapy · doi:10.2147/ott.s98488 · Cited by 18 · see citing works
de Nałęcz, A. K., Ciszak, L., Usnarska‐Zubkiewicz, L., Frydecka, I., Pawlak, E., Szmyrka−Kaczmarek, M., & Kosmaczewska, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179298 · Cited by 18 · see citing works
Decoding T cell senescence in cancer: Is revisiting required?
Magkouta, S., Markaki, E., Evangelou, K., Petty, R., Verginis, P., & Gorgoulis, V. G. (2024) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2024.11.003 · Cited by 17 · see citing works
Mignot, G., Hervieu, A., Vabres, P., Dalac, S., Jeudy, G., Bel, B., Apétoh, L., & Ghiringhelli, F. (2014) · PLoS ONE · doi:10.1371/journal.pone.0105907 · Cited by 17 · see citing works
MM-BMSCs induce naïve CD4+ T lymphocytes dysfunction through fibroblast activation protein α
Wu, X., Wang, Y., Xu, J., Luo, T., Deng, J., & Hu, Y. (2017) · Oncotarget · doi:10.18632/oncotarget.17538 · Cited by 17 · see citing works
Neoadjuvant chemotherapy modulates exhaustion of T cells in breast cancer patients
Rodríguez, I. J., Bernal-Estévez, D. A., Llano-León, M., Bonilla, C., & Parra-López, C. (2023) · PLoS ONE · doi:10.1371/journal.pone.0280851 · Cited by 16 · see citing works
VLA-4 suppression by senescence signals regulates meningeal immunity and leptomeningeal metastasis
Li, J., Huang, D., Lei, B., Huang, J., Yang, L., Nie, M., Su, S., Zhao, Q., & Wang, Y. (2022) · eLife · doi:10.7554/elife.83272 · Cited by 15 · see citing works
The Role of Aging and Senescence in Immune Checkpoint Inhibitor Response and Toxicity
Jain, S. S., Sojo, G. B., Sun, H., Friedland, B. N., McNamara, M. E., Schmidt, M. O., & Wellstein, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137013 · Cited by 16 · see citing works
Das, J. K., Ren, Y., Kumar, A., Peng, H., Wang, L., Xiong, X., Alaniz, R. C., de Figueiredo, P., Ren, X., Liu, X., et al. (2022) · Science Advances · doi:10.1126/sciadv.abl9783 · Cited by 14 · see citing works
Characteristics and mechanisms of T‐cell senescence: A potential target for cancer immunotherapy
Wu, H., Li, J., Zhang, Z., & Zhang, Y. (2024) · European Journal of Immunology · doi:10.1002/eji.202451093 · Cited by 14 · see citing works
Shi, H., Xiao, M., Li, Y., Liu, X., Na, J., Liang, C., Hua, J., Meng, Q., Wei, M., Wang, W., et al. (2025) · Theranostics · doi:10.7150/thno.112633 · Cited by 12 · see citing works
CD8+ T cell stressors converge on shared metabolic–epigenetic networks
Shangguan, Y., Wang, J., Ho, P., & Xu, Y. (2025) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2025.08.009 · Cited by 13 · see citing works
Alloimmune Responses and Atherosclerotic Disease After Kidney Transplantation
Ducloux, D., Courivaud, C., Bamoulid, J., Bisaccia, V., Roubiou, C., Crépin, T., Gaugler, B., Laheurte, C., Rebibou, J.-M., Chalopin, J., et al. (2014) · Transplantation · doi:10.1097/tp.0000000000000346 · Cited by 12 · see citing works
Chen, Y., Yim, W. Y., Li, C., Wang, Z., Hou, J., Peng, Y., Liu, F., Liu, Z., Dong, N., & Wang, Y. (2026) · Molecular Therapy · doi:10.1016/j.ymthe.2026.02.015 · Cited by 11 · see citing works
Zhang, S., Zheng, Y., Li, X., Zhang, S., Hu, H., & Kuang, W. (2023) · Aging · doi:10.18632/aging.204658 · Cited by 11 · see citing works
Phoon, Y. P., Tannenbaum, C. S., & Diaz-Montero, C. M. (2021) · Clinics in Plastic Surgery · doi:10.1016/j.cps.2021.06.005 · Cited by 12 · see citing works
Immunosenescence: Molecular Mechanisms, Diseases, and Therapeutic Innovations
Gong, N., Pan, X., Deng, Y., Che, J., Bao, J., Wang, M., Xu, C., Liu, X., & Shi, Y. (2025) · MedComm · doi:10.1002/mco2.70515 · Cited by 12 · see citing works
Overexpressing S100A9 ameliorates NK cell dysfunction in estrogen receptor-positive breast cancer
Liu, Y., Li, M., Fang, Z., Gao, S., Cheng, W., Duan, Y., Wang, X., Feng, J., Yu, T., Zhang, J., et al. (2024) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-024-03699-1 · Cited by 9 · see citing works
Kinney, B. L. C., Brammer, B., Kansal, V., Parrish, C. J., Kissick, H. T., Liu, Y., Saba, N. F., Buchwald, Z. S., El‐Deiry, M. W., Patel, M. R., et al. (2024) · OncoImmunology · doi:10.1080/2162402x.2024.2367777 · Cited by 8 · see citing works
Phoon, Y. P., Lopes, J. E., Pfannenstiel, L. W., Diaz-Montero, C. M., Tian, Y. F., Ernstoff, M. S., Funchain, P., Ko, J. S., Winquist, R. J., Losey, H. C., et al. (2024) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2023-008066 · Cited by 5 · see citing works
Self-citationNewly emerging standard chemotherapies for gastric cancer and clinical potential in elderly patients
Sakuramoto, S. (2009) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v1.i1.47 · Cited by 5 · see citing works
Multiple characteristic alterations and available therapeutic strategies of cellular senescence
Zhao, Y., Li, H., Guo, Q., & Hui, H. (2023) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.b2200178 · Cited by 5 · see citing works
The effects of tumor‐derived exosomes on T‐cell function and efficacy of cancer immunotherapy
Hao, Y., Chen, P., Zhang, X., Shao, Y., Xu, Y. Y., & Qian, W. (2021) · ImmunoMedicine · doi:10.1002/imed.1029 · Cited by 5 · see citing works
Self-citationHua, H., Zheng, C., Fan, J., Li, X., Xie, W., Chen, J., & Yu, C. (2022) · BioMed Research International · doi:10.1155/2022/1916787 · Cited by 4 · see citing works
Kourelis, T., Jevremović, D., Jessen, E., Dasari, S., Villasboas, J. C., Dispenzieri, A. A., & Kumar, S. K. (2020) · British Journal of Haematology · doi:10.1111/bjh.16522 · Cited by 4 · see citing works
- Authors
- Montes, C. L., Chapoval, A. I., Nelson, J., Orhue, V., Zhang, X., Schulze, D. H., Strome, S. E., & Gastman, B. R.
- Affiliations
- 1Department of Otorhinolaryngology and
- University of Maryland, Baltimore (US)
- ORCID
- Venue
- Cancer Research
- Published
- 2008-02-01
- Volume
- 68
- Issue
- 3
- Pages
- 870-879
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W1979003707
- Cited by
- 127
- References
- 50
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 12 · 2023: 11 · 2022: 13 · 2021: 20 · 2020: 6 · 2019: 4 · 2018: 3 · 2017: 5 · 2016: 5 · 2015: 6 · 2014: 6 · 2013: 7 · 2012: 3
- FWCI
- 1.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- T cell senescence, regulatory T cells, tumor immune evasion, antitumor immunity, CD27, CD28, telomere shortening, p53, p21, p16, T cell proliferation inhibition, cell-cell contact, CD4+ T cells, CD8+ T cells, natural regulatory T cells
- MeSH terms
- Adult, DNA Damage, Humans, Lymphocyte Activation, Neoplasms, CD4-Positive T-Lymphocytes, Cellular Senescence, In Situ Hybridization, Fluorescence, CD8-Positive T-Lymphocytes, Cell Cycle Proteins, Tumor Escape, Jurkat Cells, Cell Line, Tumor, T-Lymphocytes, Regulatory
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