TLR8 signaling enhances tumor immunity by preventing tumor‐induced T‐cell senescence
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Accumulating evidence suggests the immunosuppressive microenvironments created by malignant tumors represent a major obstacle for effective anti‐tumor immunity. A better understanding of the suppressive mechanisms mediated by tumor microenvironments and the development of strategies to reverse the immune suppression are major challenges for the success of tumor immunotherapy. Here, we report that human tumor cells can induce senescence in naïve/effector T cells, exhibiting potent suppressive function in vitro and in vivo . We further show that tumor‐derived endogenous cyclic adenosine monophosphate (cAMP) is responsible for the induction of T‐cell senescence. Importantly, activation of TLR8 signaling in tumor cells can block the induction and reverse the suppression of senescent naïve and tumor‐specific T cells in vitro and in vivo , resulting in enhanced anti‐tumor immunity. These studies identify a novel mechanism of human tumor‐mediated immune suppression and provide a new strategy to reverse tumor immunosuppressive effects for tumor immunotherapy.
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Activation of Toll-like receptor 8 signaling in tumor cells can enhance antitumor immunity by blocking the induction of senescent T cells and tumor-specific T cells in vitro and in vivo and reversing their inhibitory effect.
“Furthermore, the activation of Toll-like receptor 8 signaling in tumor cells can enhance antitumor immunity by blocking the induction of senescent T cells and tumor-specific T cells in vitro and in vivo and reversing their inhibitory effect [63].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [63]
Tumor cells activate the PKA-CREB and P38 pathways by producing cAMP, thereby causing DNA damage and senescence of T cells.
“In addition, tumor cells activate the PKA-CREB and P38 pathways by producing cAMP, thereby causing DNA damage and senescence of T cells [51, 53, 58–63].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [63]
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The limited in vitro lifetime of human diploid cell strains
Hayflick, L. (1965) · Experimental Cell Research · doi:10.1016/0014-4827(65)90211-9 · Cited by 5,876 · see citing works
Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion
Dong, H., Strome, S. E., Salomao, D. R., Tamura, H., Hirano, F., Flies, D. B., Roche, P. C., Lu, J., Zhu, G., Tamada, K., et al. (2002) · Nature Medicine · doi:10.1038/nm730 · Cited by 5,025 · see citing works
Cellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441 · see citing works
Cancer immunotherapy: moving beyond current vaccines
Rosenberg, S. A., Yang, J. C.-H., & Restifo, N. P. (2004) · Nature Medicine · doi:10.1038/nm1100 · Cited by 2,956 · see citing works
The tumor microenvironment and its role in promoting tumor growth
Whiteside, T. L. (2008) · Oncogene · doi:10.1038/onc.2008.271 · Cited by 2,376 · see citing works
Uyttenhove, C., Pilotte, L., Théate, I., Stroobant, V., Colau, D., Parmentier, N., Boon, T., & Van den Eynde, B. J. (2003) · Nature Medicine · doi:10.1038/nm934 · Cited by 2,305 · see citing works
Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion
Rodier, F., Coppé, J.-P., Patil, C. K., Hoeijmakers, W. A. M., Muñoz, D. P., Raza, S. R., Freund, A., Campeau, E., Davalos, A. R., & Campisi, J. (2009) · Nature Cell Biology · doi:10.1038/ncb1909 · Cited by 2,232 · see citing works
Interleukin‐10‐secreting type 1 regulatory T cells in rodents and humans
Roncarolo, M. G., Gregori, S., Battaglia, M., Bacchetta, R., Fleischhauer, K., & Levings, M. K. (2006) · Immunological Reviews · doi:10.1111/j.0105-2896.2006.00420.x · Cited by 1,174 · see citing works
A2A adenosine receptor protects tumors from antitumor T cells
Ohta, A., Gorelik, E., Prasad, S. J., Ronchese, F., Lukashev, D. E., Wong, M. K. K., Huang, X., Caldwell, S. A., Liu, K., Smith, P. T., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605251103 · Cited by 1,066 · see citing works
Innate Immunity Gone Awry: Linking Microbial Infections to Chronic Inflammation and Cancer
Karin, M., Lawrence, T., & Nizet, V. (2006) · Cell · doi:10.1016/j.cell.2006.02.016 · Cited by 938 · see citing works
HIV-specific CD8(+) T cells produce antiviral cytokines but are impaired in cytolytic function
Appay, V., Nixon, D. F., Donahoe, S. M., Gillespie, G. M. A., Dong, T., King, A., Ogg, G. S., Spiegel, H. M. L., Conlon, C., Spina, C. A., et al. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.1.63 · Cited by 871 · see citing works
Therapeutic targeting of innate immunity with Toll-like receptor agonists and antagonists
Kanzler, H., Barrat, F. J., Hessel, E. M., & Coffman, R. L. (2007) · Nature Medicine · doi:10.1038/nm1589 · Cited by 869 · see citing works
Toll-Like Receptor 8-Mediated Reversal of CD4 + Regulatory T Cell Function
Peng, G., Guo, Z., Kiniwa, Y., Voo, K. S., Peng, W., Fu, T., Wang, D. Y., Li, Y., Wang, H. Y., & Wang, R. (2005) · Science · doi:10.1126/science.1113401 · Cited by 748 · see citing works
Self-citationQuezada, S. A. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27745 · Cited by 700 · cited 1× · see citing works
“However, these strategies can concurrently eliminate activated effector T cells, prevent effector T-cell activities, and induce Treg cell replenishment, which attenuate the effects of effector T cells on anti-tumor immunity (Colombo & Piconese, 2007; Powell et al , 2007a,b; Quezada et al , 2006).”
Cyclic adenosine monophosphate is a key component of regulatory T cell–mediated suppression
Bopp, T., Becker, C., Klein, M., Klein‐Hessling, S., Palmetshofer, A., Serfling, E., Heib, V., Becker, M., Kubach, J., Schmitt, S., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20062129 · Cited by 659 · see citing works
CD28− T cells: their role in the age-associated decline of immune function
Weng, N., Akbar, A. N., & Goronzy, J. J. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.03.013 · Cited by 630 · see citing works
Toll-Like Receptors on Tumor Cells Facilitate Evasion of Immune Surveillance
Huang, B., Zhao, J., Li, H., He, K., Chen, Y., Mayer, L. F., Unkeless, J. C., & Xiong, H. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-0784 · Cited by 542 · 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
Peng, G., Wang, H. Y., Peng, W., Kiniwa, Y., Seo, K. H., & Wang, R. (2007) · Immunity · doi:10.1016/j.immuni.2007.05.020 · Cited by 408 · see citing works
Self-citationRegulatory T-cell inhibition versus depletion: the right choice in cancer immunotherapy
Colombo, M. P., & Piconese, S. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2250 · Cited by 404 · see citing works
Goronzy, J. J., Fulbright, J. W., Crowson, C. S., Poland, G. A., O'Fallon, W. M., & Weyand, C. M. (2001) · Journal of Virology · doi:10.1128/jvi.75.24.12182-12187.2001 · Cited by 402 · see citing works
Plasmacytoid Dendritic Cells Induce CD8+ Regulatory T Cells In Human Ovarian Carcinoma
Wei, S., Kryczek, I., Zou, L., Daniel, B., Cheng, P. J., Mottram, P. J., Curiel, T. J., Lange, A., & Zou, W. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-4043 · Cited by 379 · see citing works
TLR signaling by tumor and immune cells: a double-edged sword
Huang, B., Zhao, J., Unkeless, J. C., Feng, Z., & Xiong, H. (2008) · Oncogene · doi:10.1038/sj.onc.1210904 · Cited by 377 · see citing works
CD8+ Foxp3+ Regulatory T Cells Mediate Immunosuppression in Prostate Cancer
Kiniwa, Y., Miyahara, Y., Wang, H. Y., Peng, W., Peng, G., Wheeler, T. M., Thompson, T. C., Old, L. J., & Wang, R. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-0842 · Cited by 353 · see citing works
Self-citationRole Of Immature Myeloid Cells in Mechanisms of Immune Evasion In Cancer
Kusmartsev, S. A., & Gabrilovich, D. I. (2005) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-005-0048-z · Cited by 346 · 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
Vang, T., Torgersen, K. M., Sundvold, V., Saxena, M., Levy, F. O., Skålhegg, B. S., Hansson, V., Mustelin, T., & Taskén, K. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.4.497 · Cited by 330 · see citing works
Tumor microenvironments direct the recruitment and expansion of human Th17 cells
Su, X., Ye, J., Hsueh, E. C., Zhang, Y., Hoft, D. F., & Peng, G. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0902813 · Cited by 324 · see citing works
Self-citationTumor-Selective Induction of Apoptosis and the Small-Molecule Immune Response Modifier Imiquimod
Schön, M., Bong, A. B., Drewniok, C., Herz, J., Geilen, C. C., REIFENBERGER, J., Benninghoff, B., Slade, H. B., Gollnick, H. P. M., & Schön, M. P. (2003) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djg016 · Cited by 258 · see citing works
Kavanagh, B., O'Brien, S., Lee, D., Hou, Y., Weinberg, V., Rini, B., Allison, J. P., Small, E. J., & Fong, L. (2008) · Blood · doi:10.1182/blood-2007-11-125435 · Cited by 256 · see citing works
Sitkovsky, M. V., Kjaergaard, J., Lukashev, D., & Ohta, A. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0229 · Cited by 253 · see citing works
Cherfils‐Vicini, J., Platonova, S., Gillard, M., Laurans, L., Validire, P., Caliandro, R., Magdeleinat, P., Mami‐Chouaib, F., Dieu‐Nosjean, M., Fridman, W. H., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci36551 · Cited by 238 · see citing works
Croci, D. O., Fluck, M. F. Z., Rico, M. J., Matar, P., Rabinovich, G. A., & Scharovsky, O. G. (2007) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-007-0343-y · Cited by 228 · see citing works
Vaccination in the elderly: an immunological perspective
Chen, W. H., Kozlovsky, B. F., Effros, R. B., Grubeck‐Loebenstein, B., Edelman, R., & Sztein, M. B. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.05.002 · Cited by 228 · see citing works
The Use of TLR7 and TLR8 Ligands for the Enhancement of Cancer Immunotherapy
Smits, E., Ponsaerts, P., Berneman, Z. N., & Tendeloo, V. F. V. (2008) · The Oncologist · doi:10.1634/theoncologist.2008-0097 · Cited by 216 · see citing works
Toll-like Receptor 3 Expressed by Melanoma Cells as a Target for Therapy?
Salaun, B., Lebecque, S., Matikainen, S., Rimoldi, D., & Romero, P. J. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-0274 · Cited by 204 · 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
Self-citationHuman 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
Self-citationCortesini, R., LeMaoult, J., Ciubotariu, R., & Cortesini, N. S.-F. (2001) · Immunological Reviews · doi:10.1034/j.1600-065x.2001.1820116.x · Cited by 185 · see citing works
Meloni, 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
Powell, D. J., Felipe-Silva, A., Merino, M. J., Ahmadzadeh, M., Allen, T., Levy, C. L., White, D. E., Mavroukakis, S. A., Kreitman, R. J., Rosenberg, S. A., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.7.4919 · Cited by 166 · 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
Toll-like receptors and immune regulation: implications for cancer therapy
Wang, R.-F., Miyahara, Y., & Wang, H. Y. (2008) · Oncogene · doi:10.1038/sj.onc.1210906 · Cited by 149 · see citing works
Tumor-induced senescent T cells with suppressor function: a potential form of tumor immune evasion
Montes, C. L., Chapoval, A. I., Nelson, J., Orhue, V., Zhang, X., Schulze, D. H., Strome, S. E., & Gastman, B. R. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-2282 · Cited by 127 · see citing works
Toll-like Receptors in Tumor Immunotherapy
Paulos, C. M., Kaiser, A., Wrzesinski, C., Hinrichs, C. S., Cassard, L., Boni, A., Muranski, P. J., Sanchez-Perez, L. A., Palmer, D. C., Yu, Z., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-1378 · Cited by 124 · see citing works
Regulatory T cells control HIV replication in activated T cells through a cAMP-dependent mechanism
Moreno‐Fernandez, M. E., Rueda, C. M., Rusie, L. K., & Chougnet, C. A. (2011) · Blood · doi:10.1182/blood-2010-12-323162 · Cited by 115 · see citing works
Liang, X., Moseman, E. A., Farrar, M. A., Bachanová, V., Weisdorf, D. J., Blazar, B. R., & Chen, W. (2010) · Blood · doi:10.1182/blood-2009-03-213363 · Cited by 105 · see citing works
Identifying and Overcoming Immune Resistance Mechanisms in the Melanoma Tumor Microenvironment
Gajewski, T. F. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-2517 · Cited by 97 · see citing works
Detection of T suppressor cells in patients with organ allografts
Ciubotariu, R., Vasilescu, E. R., Ho, E. K., Cinti, P., Cancedda, C., Poli, L., Late, M., Liu, Z., Berloco, P. B., Cortesini, R., et al. (2001) · Human Immunology · doi:10.1016/s0198-8859(00)00226-3 · Cited by 80 · see citing works
The molecular machinery for cAMP-dependent immunomodulation in T-cells
Taskén, K., & Stokka, A. J. (2006) · Biochemical Society Transactions · doi:10.1042/bst0340476 · Cited by 76 · see citing works
DNA damage-induced cellular senescence is sufficient to suppress tumorigenesis: a mouse model
Van Nguyen, T., Puebla-Osorio, N., Pang, H., Dujka, M. E., & Zhu, C. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20062453 · Cited by 72 · see citing works
Powell, D. J., de Vries, C. R., Allen, T., Ahmadzadeh, M., & Rosenberg, S. A. (2007) · Journal of Immunotherapy · doi:10.1097/cji.0b013e3180600ff9 · Cited by 59 · see citing works
Grader‐Beck, T., van Puijenbroek, A. A. F. L., Nadler, L. M., & Boussiotis, V. A. (2003) · Blood · doi:10.1182/blood-2002-06-1665 · Cited by 50 · see citing works
Antitumor Activity and Immune Response Induction of a Dual Agonist of Toll-Like Receptors 7 and 8
Wang, D., Precopio, M., Lan, T., Yu, D. S., Tang, J. X., Kandimalla, E. R., & Agrawal, S. (2010) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-09-1198 · Cited by 42 · see citing works
Ye, J., Ma, C., Hsueh, E. C., Zhang, Y., Varvares, M. A., Hoft, D. F., & Peng, G. (2013) · Cancer Research · doi:10.1158/1538-7445.am2013-4995 · Cited by 12 · see citing works
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Immunosenescence: a key player in cancer development
Lian, J., Yue, Y., Yu, W., & Zhang, Y. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00986-z · Cited by 510 · see citing works
Self-citationTargeting Adenosine in Cancer Immunotherapy to Enhance T-Cell Function
Viganó, S., Alatzoglou, D., Irving, M. B., Ménétrier‐Caux, C., Caux, C., Romero, P. J., & Coukos, G. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00925 · Cited by 422 · 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
Self-citationReprogramming lipid metabolism prevents effector T cell senescence and enhances tumor immunotherapy
Liu, X., Hartman, C. L., Li, L., Albert, C. J., Si, F., Gao, A., Huang, L. J., Zhao, Y., Lin, W., Hsueh, E. C., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.aaz6314 · Cited by 278 · see citing works
Self-citationT cell senescence and CAR-T cell exhaustion in hematological malignancies
Kasakovski, D., Xu, L., & Li, Y. (2018) · Journal of Hematology & Oncology · doi:10.1186/s13045-018-0629-x · Cited by 274 · see citing works
Li, L., Liu, X., Sanders, K. L., Edwards, J. L., Ye, J., Si, F., Gao, A., Huang, L., Hsueh, E. C., Ford, D. A., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.09.020 · Cited by 244 · see citing works
Self-citationTrial Watch: Toll-like receptor agonists in cancer immunotherapy
Smith, M. M., García-Martínez, E., Pitter, M. R., Fucikova, J. P., Špíšek, R., Zitvogel, L., Kroemer, G., & Galluzzi, L. (2018) · OncoImmunology · doi:10.1080/2162402x.2018.1526250 · Cited by 232 · see citing works
Regulatory T cells trigger effector T cell DNA damage and senescence caused by metabolic competition
Liu, X., Mo, W., Ye, J., Li, L., Zhang, Y., Hsueh, E. C., Hoft, D. F., & Peng, G. (2018) · Nature Communications · doi:10.1038/s41467-017-02689-5 · Cited by 224 · see citing works
Self-citationTargeting innate immune pathways for cancer immunotherapy
Cao, L. L., & Kagan, J. C. (2023) · Immunity · doi:10.1016/j.immuni.2023.07.018 · Cited by 224 · see citing works
The Evolving Role of CD8+CD28− Immunosenescent T Cells in Cancer Immunology
Huff, W. X., Kwon, J. H., Henriquez, M., Fetcko, K., & Dey, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20112810 · Cited by 217 · see citing works
Cellular senescence and the tumour microenvironment
Takasugi, M., Yoshida, Y., & Ohtani, N. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13268 · Cited by 178 · see citing works
Senescent 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
Huang, L., Xu, H., & Peng, G. (2018) · Cellular and Molecular Immunology · doi:10.1038/cmi.2018.4 · Cited by 165 · see citing works
Self-citationFigueiredo, C. R., Kalirai, H., Sacco, J. J., Azevedo, R., Duckworth, A. D., Slupsky, J. R., Coulson, J. M., & Coupland, S. E. (2020) · The Journal of Pathology · doi:10.1002/path.5384 · Cited by 146 · see citing works
Context-dependent functions of pattern recognition receptors in cancer
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Senolytics for Cancer Therapy: Is All that Glitters Really Gold?
Carpenter, V. J., Saleh, T., & Gewirtz, D. A. (2021) · Cancers · doi:10.3390/cancers13040723 · Cited by 124 · see citing works
Wei, F., Wang, D., Wei, J., Tang, N., Tang, L. M., Xiong, F., Guo, C. J., Zhou, M., Li, X., Li, G., et al. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03581-0 · Cited by 128 · see citing works
Baicalein and baicalin inhibit colon cancer using two distinct fashions of apoptosis and senescence
Dou, J., Wang, Z., Ma, L., Peng, B., Mao, K., Li, C., Su, M., Zhou, C., & Peng, G. (2018) · Oncotarget · doi:10.18632/oncotarget.24015 · Cited by 120 · see citing works
Self-citationLiu, X., Hoft, D. F., & Peng, G. (2020) · Journal of Clinical Investigation · doi:10.1172/jci133679 · Cited by 113 · see citing works
Self-citationTargeting Toll-Like Receptors for Cancer Therapy
Braunstein, M. J., Kucharczyk, J. R., & Adams, S. (2018) · Targeted Oncology · doi:10.1007/s11523-018-0589-7 · Cited by 110 · see citing works
Reshaping of the tumor microenvironment by cellular senescence: An opportunity for senotherapies
D’Ambrosio, M., & Gil, J. (2023) · Developmental Cell · doi:10.1016/j.devcel.2023.05.010 · Cited by 106 · see citing works
Li, H., Su, Q., Li, B., Lan, L., Wang, C., Li, W., Wang, G., Chen, W., He, Y., & Zhang, C. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.15104 · Cited by 107 · 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
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Pahlavanneshan, S., Sayadmanesh, A., Ebrahimiyan, H., & Basiri, M. (2021) · Journal of Immunology Research · doi:10.1155/2021/9912188 · Cited by 94 · see citing works
Ma, F., Liu, X., Zhang, Y., Tao, Y., Zhao, L., Abusalamah, H., Huffman, C., Harbison, R. A., Puram, S. V., Wang, Y., et al. (2025) · Science Translational Medicine · doi:10.1126/scitranslmed.adm7269 · Cited by 93 · see citing works
Self-citationTargeting cellular senescence in cancer and aging: roles of p53 and its isoforms
Beck, J. A., Turnquist, C., Horikawa, I., & Harris, C. C. (2020) · Carcinogenesis · doi:10.1093/carcin/bgaa071 · Cited by 94 · see citing works
Huang, F., Lei, J., Sun, Y., Yan, F., Chen, B., Zhang, L., Lu, Z., Cao, R. Y., Lin, Y., Wang, C.-C., et al. (2018) · OncoImmunology · doi:10.1080/2162402x.2018.1446720 · Cited by 90 · see citing works
Suzuki, J., Yamada, T., Inoue, K., Nabe, S., Kuwahara, M., Takemori, N., Takemori, A., Matsuda, S., Kanoh, M., Imai, Y., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05854-6 · Cited by 87 · see citing works
Zhang, F., Guo, J., Yu, S., Zheng, Y., Duan, M., Zhao, L., Wang, Y., Yang, Z., & Jiang, X. (2024) · 癌症：英文版 · doi:10.1002/cac2.12591 · Cited by 93 · see citing works
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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
Self-citationMa, C., Wang, F., Han, B., Zhong, X., Si, F., Ye, J., Hsueh, E. C., Robbins, L., Kiefer, S. M., Zhang, Y., et al. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0824-y · Cited by 80 · see citing works
Self-citationTan, T. C. J., Knight, J. R. P., Sbarrato, T., Dudek, K., Willis, A. E., & Zamoyska, R. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1700939114 · Cited by 76 · see citing works
NK and NKT cells have distinct properties and functions in cancer
Liu, X., Li, L., Si, F., Huang, L., Zhao, Y., Zhang, C., Hoft, D. F., & Peng, G. (2021) · Oncogene · doi:10.1038/s41388-021-01880-9 · Cited by 78 · see citing works
Self-citationWu, Z., Uhl, B., Gires, O., & Reichel, C. A. (2023) · Journal of Biomedical Science · doi:10.1186/s12929-023-00915-5 · Cited by 78 · see citing works
Controlling T cell senescence in the tumor microenvironment for tumor immunotherapy
Ye, J., & Peng, G. (2015) · OncoImmunology · doi:10.4161/2162402x.2014.994398 · Cited by 76 · see citing works
Self-citationThe senescence journey in cancer immunoediting
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
Xiong, Y., Xiong, Y., Zhang, H., Zhao, Y., Han, K., Zhang, J., Zhao, D., Yu, Z., Geng, Z., Wang, L., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.780897 · Cited by 69 · see citing works
Silva, C. G. D., Camps, M. G. M., Li, T. M. W. Y., Zerrillo, L., Löwik, C. W. G. M., OSSENDORP, F. A., & Cruz, L. J. (2019) · Theranostics · doi:10.7150/thno.34429 · Cited by 69 · see citing works
Senescent stromal cells: roles in the tumor microenvironment
Gabai, Y., Assouline, B., & Ben‐Porath, I. (2022) · Trends in cancer · doi:10.1016/j.trecan.2022.09.002 · Cited by 63 · see citing works
Senescence in the Development and Response to Cancer with Immunotherapy: A Double-Edged Sword
Battram, A. M., Bachiller, M., & Martín-Antonio, B. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124346 · Cited by 63 · see citing works
Toll-like receptor-targeted anti-tumor therapies: Advances and challenges
Yang, Y., Li, H., Fotopoulou, C., Cunnea, P., & Zhao, X. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1049340 · Cited by 60 · see citing works
Citrate Promotes Excessive Lipid Biosynthesis and Senescence in Tumor Cells for Tumor Therapy
Zhao, Y., Liu, X., Si, F., Huang, L., Gao, A., Lin, W., Hoft, D. F., Shao, Q., & Peng, G. (2021) · Advanced Science · doi:10.1002/advs.202101553 · Cited by 57 · see citing works
Self-citationSenescence and tumor suppression
Hinds, P. W., & Pietruska, J. R. (2017) · F1000Research · doi:10.12688/f1000research.11671.1 · Cited by 57 · 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
ILT4 functions as a potential checkpoint molecule for tumor immunotherapy
Gao, A., Sun, Y., & Peng, G. (2018) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2018.04.001 · Cited by 56 · see citing works
Self-citationT-cell abnormalities in common variable immunodeficiency: the hidden defect
Wong, G. K. Y., & Huissoon, A. P. (2016) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2015-203351 · Cited by 53 · see citing works
Baicalein and Baicalin Promote Melanoma Apoptosis and Senescence via Metabolic Inhibition
Huang, L., Peng, B., Nayak, Y. R., Wang, C., Si, F., Liu, X., Dou, J., Xu, H., & Peng, G. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00836 · Cited by 51 · see citing works
Self-citationSenescent cells in cancer therapy: why and how to remove them
Zhang, J., Zhang, D., & Yu, B. (2021) · Cancer Letters · doi:10.1016/j.canlet.2021.07.002 · Cited by 50 · see citing works
T-cell senescence accelerates angiotensin II-induced target organ damage
Pan, X., Wu, F., Chen, X.-H., Chen, D.-R., Chen, H., Kong, L., Ruan, C., & Gao, P. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvaa032 · Cited by 49 · 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
Toll-Like Receptors in Adaptive Immunity
Kumar, V. (2021) · Handbook of experimental pharmacology · doi:10.1007/164_2021_543 · Cited by 46 · see citing works
Litak, J., Grochowski, C., Litak, J., Osuchowska, I., Gosik, K., Radzikowska, E., Kamieniak, P., & Roliński, J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093114 · Cited by 47 · see citing works
Cellular senescence and hematological malignancies: From pathogenesis to therapeutics
Hu, D., Yuan, S., Zhong, J., Liu, Z., Wang, Y., Liu, L., Li, J., Wen, F., Liu, J., & Zhang, J. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107817 · Cited by 45 · see citing works
Tumor microenvironment metabolites directing T cell differentiation and function
Liu, X., Hoft, D. F., & Peng, G. (2021) · Trends in Immunology · doi:10.1016/j.it.2021.12.004 · Cited by 44 · see citing works
Self-citationRamello, M. C., Núñez, N. G., Tosello, J., Bossio, S., Canale, F. P., Abrate, C. P., Ponce, N. E., del Castillo, A., Ledesma, M., Viel, S., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.713132 · Cited by 43 · see citing works
Age-related decline in CD8+ tissue resident memory T cells compromises antitumor immunity
Pei, S., Deng, X., Yang, R., Wang, H., Shi, J., Wang, X., Huang, J., Tian, Y., Wang, R., Zhang, S., et al. (2024) · Nature Aging · doi:10.1038/s43587-024-00746-5 · Cited by 42 · see citing works
Self-citationHuo, Y., Zhou, Y., Zheng, J.-H., Jin, G., Tao, L., Yao, H., Zhang, J., Sun, Y., Liu, Y., & Hu, L.-P. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.983116 · Cited by 38 · see citing works
Immunotherapeutic strategies in head and neck cancer: challenges and opportunities
Liu, X., Harbison, R. A., Varvares, M. A., Puram, S. V., & Peng, G. (2025) · Journal of Clinical Investigation · doi:10.1172/jci188128 · Cited by 38 · see citing works
Self-citationT 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
TLR7 Signaling Regulates Th17 Cells and Autoimmunity: Novel Potential for Autoimmune Therapy
Ye, J., Wang, Y., Liu, X., Li, L., Opejin, A., Hsueh, E. C., Luo, H., Wang, T., Hawiger, D., & Peng, G. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1601890 · Cited by 35 · see citing works
Self-citationBiomechanics 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 32 · see citing works
The role of novel immunotherapies in non-Hodgkin lymphoma
Pishko, A. M., & Nasta, S. D. (2017) · Translational Cancer Research · doi:10.21037/tcr.2017.01.08 · Cited by 32 · see citing works
Si, F., Liu, X., Tao, Y., Zhang, Y., Ma, F., Hsueh, E. C., Puram, S. V., & Peng, G. (2024) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2023-008219 · Cited by 31 · see citing works
Self-citationMetabolic reprogramming in T cell senescence: a novel strategy for cancer immunotherapy
Liu, L., Hao, Z., Yang, X., Li, Y., Wang, S., & Li, L. (2025) · Cell Death Discovery · doi:10.1038/s41420-025-02468-y · Cited by 30 · see citing works
Zhong, Z., Hong, M. H., Chen, X., Xi, Y., Xu, Y., Kong, D., Deng, J., Li, Y., Hu, R., Sun, C., et al. (2020) · BMC Medical Genomics · doi:10.1186/s12920-020-0707-0 · Cited by 30 · see citing works
Xiong, Y., WANG, Y., Zhang, J., Zhao, N., Zhang, A., Zhang, A., Zhao, D., Yu, Z., Yin, Y., Song, L., et al. (2020) · Stem Cell Research & Therapy · doi:10.1186/s13287-020-01993-0 · Cited by 29 · see citing works
Harnessing Metabolic Reprogramming to Improve Cancer Immunotherapy
Liang, Y., Tan, Y., Chen, G., Fan, J., & Zhang, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910268 · Cited by 28 · see citing works
T-cell Senescence in the Tumor Microenvironment
Huang, L., Zhang, C., Jiang, A., Lin, A., Zhu, L., Mou, W., Zeng, D., Liu, Z., Tang, B., Zhang, J., et al. (2025) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-24-0894 · Cited by 27 · see citing works
Hu, M. Y., Zhang, J., Yu, Y., Tu, K., Yang, T., Wang, Y., Hu, Q., Kong, L., & Zhang, Z. (2020) · Small · doi:10.1002/smll.202004905 · Cited by 26 · see citing works
Tumor Secretome to Adoptive Cellular Immunotherapy: Reduce Me Before I Make You My Partner
Etxebeste-Mitxeltorena, M., del Rincón-Loza, I., & Martín-Antonio, B. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.717850 · Cited by 25 · 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
Fu, T., Jin, X., He, M., Chen, Y.-Y., Yang, Y.-S., Chen, L., Zhang, H.-Y.-L., Fan, L., Wu, J., Wang, Z.-H., et al. (2025) · Science Translational Medicine · doi:10.1126/scitranslmed.adj7808 · Cited by 24 · see citing works
Emerging role of RNA sensors in tumor microenvironment and immunotherapy
Yang, R. Y., Yu, S., Xu, T., Zhang, J., & Wu, S. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01261-z · Cited by 26 · see citing works
Torres, F., Leon, S., Ummarino, A., Redín, E., Allavena, P., Serrano, D., Anfray, C., & Calvo, A. (2022) · Biomedicines · doi:10.3390/biomedicines10071590 · Cited by 24 · 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
Toll-like receptors in breast cancer immunity and immunotherapy
Zhou, J., Zhang, L., Liu, S., DeRubeis, D., & Zhang, D. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1418025 · Cited by 23 · see citing works
Self-citationVeld, R. V. H. I. ‘., Silva, C. G. D., Jager, M. J., Cruz, L. J., & OSSENDORP, F. A. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13091470 · Cited by 23 · see citing works
Gut microbiota and immunosenescence in cancer
Xu, Y., He, C., Xi, Y., Zhang, Y., & Bai, Y. (2024) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2024.07.004 · Cited by 22 · see citing works
Self-citationImmunosenescence and age-related immune cells: causes of age-related diseases
Kim, N., Sim, S.-J., Han, H.-G., Yoon, J.-H., & Han, Y. (2024) · Archives of Pharmacal Research · doi:10.1007/s12272-024-01529-7 · Cited by 21 · see citing works
Towers, R., Trombello, L., Fusenig, M., Tunger, A., Baumann, A.-L., Savoldelli, R., Wehner, R., Faßlrinner, F., Arndt, C., Dazzi, F., et al. (2024) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-023-03594-1 · Cited by 21 · see citing works
Immunosenescence: A new direction in anti-aging research
Li, H., Lin, S., Wang, Y., Shi, Y., Fang, X., Wang, J., Cui, H., Bian, Y., & Qi, X. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.112900 · Cited by 21 · see citing works
Angrini, M., Varthaman, A., & Cremer, I. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-44518-8_9 · Cited by 20 · see citing works
Accumulation of CD28null Senescent T-Cells Is Associated with Poorer Outcomes in COVID19 Patients
Coleman, M. J., Zimmerly, K. M., & Yang, X. O. (2021) · Biomolecules · doi:10.3390/biom11101425 · Cited by 20 · see citing works
Topically Applied Resiquimod versus Imiquimod as a Potential Adjuvant in Melanoma Treatment
Tambunlertchai, S., Geary, S. M., & Salem, A. K. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14102076 · Cited by 19 · see citing works
Liu, J., Zheng, R., Zhang, Y., Jia, S., He, Y., & Liu, J. (2023) · Cancers · doi:10.3390/cancers15092640 · Cited by 19 · see citing works
Self-citationImplications of Senescent T Cells for Cancer Immunotherapy
Kasamatsu, T. (2023) · Cancers · doi:10.3390/cancers15245835 · Cited by 20 · see citing works
From infection to immune exhaustion: The Epstein-Barr virus and its contribution to Immunosenescence
Hu, L., Zhu, T., Long, J., Luo, Q., & Lyu, X. (2025) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2025.189421 · Cited by 19 · 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
Fungi, immunosenescence and cancer
Xu, B., Luo, Z., Niu, X., Li, Z., Lu, Y., & Li, J. (2025) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2025.01.002 · Cited by 17 · see citing works
Shukla, S., Kumari, S., Bal, S. K., Mónaco, D. C., Ribeiro, S. P., Sékaly, R., & Sharma, A. (2021) · Current Opinion in HIV and AIDS · doi:10.1097/coh.0000000000000692 · 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
Yun, S. J., Lee, B., Komori, K., Lee, M. J., Lee, B. G., Kim, K. H., & Park, S. (2018) · Molecular Immunology · doi:10.1016/j.molimm.2018.12.006 · Cited by 17 · see citing works
Recent Advances in the Aging Microenvironment of Breast Cancer
Jiang, X., Shen, H., Xi, S., Fang, J., Lu, Y., Lu, Y., Zheng, J., & Fu, P. (2022) · Cancers · doi:10.3390/cancers14204990 · Cited by 16 · see citing works
The Tumor Microenvironment Reprograms Immune Cells
Cao, H., Gao, S., Jogani, R., & Sugimura, R. (2022) · Cellular Reprogramming · doi:10.1089/cell.2022.0047 · Cited by 16 · see citing works
Participation of T cells in generating immune protection against cancers
Deo, A. S., Shrijana, Sruthika, S. U., Karun, S., Bisaria, K., & Sarkar, K. (2024) · Pathology - Research and Practice · doi:10.1016/j.prp.2024.155534 · 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
- Authors
- Ye, J., Ma, C., Hsueh, E. C., Dou, J., Mo, W., Liu, S., Han, B., Huang, Y., Zhang, Y., Varvares, M. A., Hoft, D. F., & Peng, G.
- Affiliations
- Saint Louis University (US)
- Corresponding author
- Peng, Guangyong
- ORCID
- Venue
- EMBO Molecular Medicine
- Published
- 2014-09-17
- Volume
- 6
- Issue
- 10
- Pages
- 1294-1311
- ISSN
- 1757-4676 (ISSN-L)
- 1757-4684
- PMC
- PMC4287933
- OpenAlex
- W2000656984
- Cited by
- 161
- References
- 56
- Citations by year
- 2026: 6 · 2025: 24 · 2024: 24 · 2023: 14 · 2022: 16 · 2021: 27 · 2020: 22 · 2019: 6 · 2018: 13 · 2017: 5 · 2016: 1 · 2015: 3
- FWCI
- 1.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- EMBO Molecular Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- American Cancer Society (RSG‐10‐160‐01‐LIB)
- Melanoma Research Alliance
- National Institutes of Health
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- T cell senescence, tumor immunosuppression, tumor microenvironment, cyclic AMP, antitumor immunity, cancer immunotherapy, tumor-specific T cells
- MeSH terms
- Cyclic AMP, Animals, Cells, Cultured, Flow Cytometry, Humans, Neoplasms, T-Lymphocytes, Blotting, Western, Signal Transduction, CD4-Positive T-Lymphocytes, Immunotherapy, Adoptive, Mice, SCID, Mice, Inbred NOD, Cellular Senescence, Mice, Knockout, Coculture Techniques, Xenograft Model Antitumor Assays, RNA Interference, Cell Line, Tumor, Toll-Like Receptor 8, Interleukin Receptor Common gamma Subunit, Tumor Microenvironment, MCF-7 Cells
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