Targetable mechanisms driving immunoevasion of persistent senescent cells link chemotherapy-resistant cancer to aging
Open accessAbstract
Cellular senescence is a tumor-suppressive mechanism that can paradoxically contribute to aging pathologies. Despite evidence of immune clearance in mouse models, it is not known how senescent cells (SnCs) persist and accumulate with age or in tumors in individuals. Here, we identify cooperative mechanisms that orchestrate the immunoevasion and persistence of normal and cancer human SnCs through extracellular targeting of natural killer receptor signaling. Damaged SnCs avoided immune recognition through MMP-dependent shedding of NKG2D ligands reinforced via paracrine suppression of NKG2D receptor–mediated immunosurveillance. These coordinated immunoediting processes were evident in residual, drug-resistant tumors from cohorts of more than 700 prostate and breast cancer patients treated with senescence-inducing genotoxic chemotherapies. Unlike in mice, these reversible senescence subversion mechanisms were independent of p53/p16 and exacerbated in oncogenic RAS-induced senescence. Critically, the p16 INK4A tumor suppressor could disengage the senescence growth arrest from the damage-associated immune senescence program, which was manifest in benign nevus lesions, where indolent SnCs accumulated over time and preserved a non-proinflammatory tissue microenvironment maintaining NKG2D-mediated immunosurveillance. Our study shows how subpopulations of SnCs elude immunosurveillance and reveals potential secretome-targeted therapeutic strategies to selectively eliminate — and restore the clearance of — the detrimental SnCs that actively persist after chemotherapy and accumulate at sites of aging pathologies.
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Senescence is an important mechanism of efficacy in the treatment of breast cancer with PARP inhibitors and many typical chemotherapy agents used to treat breast cancer, such as epirubicin and cyclophosphamide.
“Senescence is also an important mechanism of efficacy in the treatment of breast cancer with PARP inhibitors [59] and many typical chemotherapy agents used to treat breast cancer, such as epirubicin and cyclophosphamide [60].”
From Senescence and Cancer: A Review of Clinical Implications of Senescence and Senotherapies (2020) · cites this paper as [60]
At younger ages, senescent cells are cleared by the host immune system.
“At younger ages, senescent cells are cleared by the host immune system [63–66]”
From Reducing Senescent Cell Burden in Aging and Disease (2020) · cites this paper as [63]
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A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477 · see citing works
Cancer immunoediting: from immunosurveillance to tumor escape
Dunn, G. P., Bruce, A. T., Ikeda, H., Old, L. J., & Schreiber, R. D. (2002) · Nature Immunology · doi:10.1038/ni1102-991 · Cited by 5,393 · see citing works
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670 · see citing works
Aging, Cellular Senescence, and Cancer
Campisi, J. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183653 · Cited by 2,954 · cited 5× · see citing works
“relevant in adult organisms, where retaining arrested yet functional cells may help maintain tissue homeostasis (1, 3, 63, 64).”
InfluentialSelf-citationNaturally occurring p16Ink4a-positive cells shorten healthy lifespan
Baker, D. J., Childs, B. G., Durik, M., Wijers, M. E., Sieben, C. J., Zhong, J., A. Saltness, R., Jeganathan, K. B., Verzosa, G. C., Pezeshki, A., et al. (2016) · Nature · doi:10.1038/nature16932 · Cited by 2,891 · see citing works
Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas
Xue, W., Zender, L., Miething, C., Dickins, R. A., Hernando, E., Krizhanovsky, V., Cordon-Cardo, C., & Lowe, S. W. (2007) · Nature · doi:10.1038/nature05529 · Cited by 2,473 · 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
Self-citationBRAFE600-associated senescence-like cell cycle arrest of human naevi
Michaloglou, C., Vredeveld, L. C. W., Soengas, M. S., Denoyelle, C., Kuilman, T., van der Horst, C. M. A. M., Majoor, D. M., Shay, J. W., Mooi, W. J., & Peeper, D. S. (2005) · Nature · doi:10.1038/nature03890 · Cited by 2,160 · see citing works
The Tumour Microenvironment after Radiotherapy: Mechanisms of Resistance and Recurrence
Barker, H. E., Paget, J. T. E., Khan, A. A., & Harrington, K. J. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3958 · Cited by 2,144 · see citing works
An Essential Role for Senescent Cells in Optimal Wound Healing through Secretion of PDGF-AA
Demaria, M., Ohtani, N., Youssef, S. A., Rodier, F., Toussaint, W., Mitchell, J. R., Laberge, R.-M., Vijg, J., Van Steeg, H., Dollé, M. E. T., et al. (2014) · Developmental Cell · doi:10.1016/j.devcel.2014.11.012 · Cited by 2,045 · see citing works
Self-citationSenescence of activated stellate cells limits liver fibrosis
Krizhanovsky, V., Yon, M., Dickins, R. A., Hearn, S., Simon, J., Miething, C., Yee, H., Zender, L., & Lowe, S. W. (2008) · Cell · doi:10.1016/j.cell.2008.06.049 · Cited by 2,029 · see citing works
Senescence of Activated Stellate Cells Limits Liver Fibrosis
Krizhanovsky, V., Yon, M., Dickins, R. A., Hearn, S., Simon, J., Miething, C., Yee, H., Zender, L., & Lowe, S. W. (2008) · Cell · doi:10.1016/j.cell.2008.09.015 · Cited by 2,027
Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints
Bartkova, J., Rezaei, N., Liontos, M., Karakaidos, P., Kletsas, D., Issaeva, N., Vassiliou, L.-V. F., Kolettas, E., Niforou, K., Zoumpourlis, V. C., et al. (2006) · Nature · doi:10.1038/nature05268 · Cited by 1,986 · see citing works
Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice
Chang, J., Wang, Y., Shao, L., Laberge, R.-M., Demaria, M., Campisi, J., Janakiraman, K., Sharpless, N. E., Ding, S., Feng, W., et al. (2016) · Nature Medicine · doi:10.1038/nm.4010 · Cited by 1,819 · see citing works
Self-citationSenescence in Health and Disease
He, S., & Sharpless, N. E. (2017) · Cell · doi:10.1016/j.cell.2017.05.015 · Cited by 1,766 · see citing works
Identifying differentially expressed genes using false discovery rate controlling procedures
Reiner, A., Yekutieli, D., & Benjamini, Y. (2003) · Bioinformatics · doi:10.1093/bioinformatics/btf877 · Cited by 1,765 · see citing works
Krtolica, A., Parrinello, S., Lockett, S., Desprez, P.-Y., & Campisi, J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.211053698 · Cited by 1,730 · see citing works
Self-citationSenescence surveillance of pre-malignant hepatocytes limits liver cancer development
Kang, T.-W., Yevsa, T., Woller, N., Hoenicke, L., Wuestefeld, T., Dauch, D., Hohmeyer, A., Gereke, M., Rudalska, R., Potapova, A., et al. (2011) · Nature · doi:10.1038/nature10599 · Cited by 1,621 · see citing works
Interferons, immunity and cancer immunoediting
Dunn, G. P., Koebel, C. M., & Schreiber, R. D. (2006) · Nature Reviews Immunology · doi:10.1038/nri1961 · Cited by 1,617 · see citing works
Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation
Groh, V., Wu, J. D., Yee, C., & Spies, T. A. (2002) · Nature · doi:10.1038/nature01112 · Cited by 1,596 · see citing works
Self-citationJeon, O. H., Kim, C., Laberge, R.-M., Demaria, M., Rathod, S., Vasserot, A. P., Chung, J. W., Kim, D. H., Poon, Y., David, N., et al. (2017) · Nature Medicine · doi:10.1038/nm.4324 · Cited by 1,515 · see citing works
Self-citationReversal of human cellular senescence: roles of the p53 and p16 pathways
Beauséjour, C. M., Krtolica, A., Galimi, F., Narita, M., Lowe, S. W., Yaswen, P., & Campisi, J. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg417 · Cited by 1,457 · see citing works
Self-citationBaar, M. P., Brandt, R. M. C., Putavet, D. A., Klein, J. D. D., Derks, K. W. J., Bourgeois, B. R. M., Stryeck, S., Rijksen, Y., van Willigenburg, H., Feijtel, D. A., et al. (2017) · Cell · doi:10.1016/j.cell.2017.02.031 · Cited by 1,454 · see citing works
Self-citationCellular senescence promotes adverse effects of chemotherapy and cancer relapse
Demaria, M., O'Leary, M. N., Chang, J., Shao, L., Liu, S., Alimirah, F., Koenig, K., Le, C., Mitin, N., Deal, A. M., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0241 · Cited by 1,338 · see citing works
Self-citationCytoplasmic chromatin triggers inflammation in senescence and cancer
Dou, Z., Ghosh, K., Vizioli, M. G., Zhu, J., Sen, P., Wangensteen, K. J., Simithy, J., Lan, Y., Lin, Y., Zhou, Z., et al. (2017) · Nature · doi:10.1038/nature24050 · Cited by 1,335 · see citing works
The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor
Gasser, S., Orsulic, S., Brown, E. J., & Raulet, D. H. (2005) · Nature · doi:10.1038/nature03884 · Cited by 1,308 · see citing works
Self-citationSenescent cells: an emerging target for diseases of ageing
Childs, B. G., Gluscevic, M., Baker, D. J., Laberge, R.-M., Marquess, D., Dananberg, J., & van Deursen, J. M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.116 · Cited by 1,284 · see citing works
Controlling Natural Killer Cell Responses: Integration of Signals for Activation and Inhibition
Long, E. O., Kim, H. S., Liu, D., Peterson, M., & Rajagopalan, S. (2013) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075005 · Cited by 1,209 · see citing works
Senescent intimal foam cells are deleterious at all stages of atherosclerosis
Childs, B. G., Baker, D. J., Wijshake, T., Conover, C. A., Campisi, J., & van Deursen, J. M. (2016) · Science · doi:10.1126/science.aaf6659 · Cited by 1,195 · see citing works
Self-citationLaberge, R.-M., Sun, Y., Orjalo, A. V., Patil, C. K., Freund, A., Zhou, L., Curran, S. C., Davalos, A. R., Wilson-Edell, K. A., Liu, S., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3195 · Cited by 1,160 · see citing works
Self-citationNK cells and cancer: you can teach innate cells new tricks
Morvan, M. G., & Lanier, L. L. (2015) · Nature reviews. Cancer · doi:10.1038/nrc.2015.5 · Cited by 1,159 · see citing works
Senescence in tumours: evidence from mice and humans
Collado, M., & Serrano, M. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2772 · Cited by 1,124 · cited 1× · see citing works
“This also raises the possibility that p16 can prevent tumor formation not only by triggering senescence arrest as an early sensor of cellular stress (65), but also by precluding the induction of immune signals that may become detrimental over time if unresolved or unwarranted.”
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
Chien, Y., Scuoppo, C., Wang, X., Fang, X., Balgley, B., Bolden, J. E., Premsrirut, P., Luo, W., Chicas, A., Lee, C. S., et al. (2011) · Genes & Development · doi:10.1101/gad.17276711 · Cited by 1,046 · see citing works
Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL
Yosef, R., Pilpel, N., Tokarsky-Amiel, R., Biran, A., Ovadya, Y., Cohen, S., Vadai, E., Dassa, L., Shahar, E., Condiotti, R., et al. (2016) · Nature Communications · doi:10.1038/ncomms11190 · Cited by 1,032 · see citing works
Jun, J.-I., & Lau, L. F. (2010) · Nature Cell Biology · doi:10.1038/ncb2070 · Cited by 998 · see citing works
Regulation of Ligands for the NKG2D Activating Receptor
Raulet, D. H., Gasser, S., Gowen, B. G., Deng, W., & Jung, H. (2013) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032712-095951 · Cited by 850 · see citing works
Self-citationSun, Y., Campisi, J., Higano, C., Beer, T. M., Porter, P., Coleman, I., True, L., & Nelson, P. S. (2012) · Nature Medicine · doi:10.1038/nm.2890 · Cited by 793 · see citing works
Self-citationRoos, C. M., Zhang, B., Palmer, A. K., Ogrodnik, M. B., Pirtskhalava, T., Thalji, N. M., Hagler, M., Jurk, D., Smith, L. A., Casaclang‐Verzosa, G., et al. (2016) · Aging Cell · doi:10.1111/acel.12458 · Cited by 738 · see citing works
Mamessier, É., Sylvain, A., Thibult, M., Houvenaeghel, G. F., Jacquemier, J. D., Castellano, R., Gonçalvès, A., André, P., Romagné, F., Thibault, G., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci45816 · Cited by 682 · see citing works
Eggert, T., Wolter, K., Ji, J., Ma, C., Yevsa, T., Klotz, S., Medina-Echeverz, J., Longerich, T., Forgues, M., Reisinger, F., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.09.003 · Cited by 609 · see citing works
Cerwenka, A., Baron, J. L., & Lanier, L. L. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.201238598 · Cited by 606 · see citing works
Lee, J.-C., Lee, K., Kim, D., & Heo, D. S. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.12.7335 · Cited by 549 · see citing works
Rodier, F., Muñoz, D. P., Teachenor, R., Chu, V., Le, O., Bhaumik, D., Coppé, J.-P., Campeau, E., Beauséjour, C. M., Kim, S.-H., et al. (2011) · Journal of Cell Science · doi:10.1242/jcs.071340 · Cited by 535 · see citing works
Self-citationNovel Genes Associated with Malignant Melanoma but not Benign Melanocytic Lesions
Talantov, D., Mazumder, A., Yu, J. X., Briggs, T., Jiang, Y., Backus, J., Atkins, D., & Wang, Y. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-0683 · Cited by 522 · see citing works
Cellular senescence in brain aging and neurodegenerative diseases: evidence and perspectives
Baker, D. J., & Petersen, R. C. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95145 · Cited by 514 · see citing works
Coppé, J.-P., Rodier, F., Patil, C. K., Freund, A., Desprez, P.-Y., & Campisi, J. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.257071 · Cited by 506 · see citing works
Self-citationStromal senescence establishes an immunosuppressive microenvironment that drives tumorigenesis
Ruhland, M. K., Loza, A. J., Capietto, A.-H., Luo, X., Knolhoff, B. L., Flanagan, K. C., Belt, B. A., Alspach, E., Leahy, K., Luo, J., et al. (2016) · Nature Communications · doi:10.1038/ncomms11762 · Cited by 496 · see citing works
Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell–driven tumor immunity
de Andrade, L. F., Tay, R. E., Pan, D., Luoma, A., Ito, Y., Badrinath, S., Tsoucas, D. M., Franz, B., May, K. F., Harvey, C. J., et al. (2018) · Science · doi:10.1126/science.aao0505 · Cited by 464 · see citing works
Soriani, A., Zingoni, A., Cerboni, C., Iannitto, M. L., Ricciardi, M. R., Di Gialleonardo, V., Cippitelli, M., Fionda, C., Petrucci, M. T., Guarini, A., et al. (2009) · Blood · doi:10.1182/blood-2008-08-173914 · Cited by 460 · see citing works
Oppenheim, D. E., Roberts, S. J., Clarke, S. L., Filler, R. B., Lewis, J., Tigelaar, R. E., Girardi, M., & Hayday, A. (2005) · Nature Immunology · doi:10.1038/ni1239 · Cited by 456 · see citing works
Coppé, J.-P., Patil, C. K., Rodier, F., Krtolica, A., Beauséjour, C. M., Parrinello, S., Hodgson, J. G., Chin, K., Desprez, P.-Y., & Campisi, J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009188 · Cited by 455 · see citing works
Self-citationMultiple roles of the cell cycle inhibitor p21CDKN1A in the DNA damage response
Cazzalini, O., Scovassi, A. I., Savio, M., Stivala, L. A., & Prosperi, E. (2010) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2010.01.009 · Cited by 430 · see citing works
DNA Damage-Mediated Induction of a Chemoresistant Niche
Gilbert, L. A., & Hemann, M. T. (2010) · Cell · doi:10.1016/j.cell.2010.09.043 · Cited by 428 · see citing works
BRD4 Connects Enhancer Remodeling to Senescence Immune Surveillance
Tasdemir, N., Banito, A., Roe, J.-S., Alonso-Curbelo, D., Camiolo, M., Tschaharganeh, D. F., Huang, C.-H., Aksoy, O., Bolden, J. E., Chen, C.-C., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0217 · Cited by 415 · cited 1× · see citing works
“So, therapeutic manipulations dampening the SASP, such as inhibitors of BET motifs (9), NF-κB (78), mTOR (79), or cGAS/STING signaling (80), may mitigate the detrimental effects of residual SnCs and restore tumor immunosurveillance.”
Iannello, A., Thompson, T. W., Ardolino, M., Lowe, S. W., & Raulet, D. H. (2013) · Journal of Experimental Medicine · doi:10.1084/jem.20130783 · Cited by 414 · see citing works
Self-citationSenescent cells and osteoarthritis: a painful connection
Jeon, O. H., David, N. E., Campisi, J., & Elisseeff, J. H. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95147 · Cited by 354 · see citing works
Self-citationp16Ink4a-induced senescence of pancreatic beta cells enhances insulin secretion
Helman, A., Klochendler, A., Azazmeh, N., Gabai, Y., Horwitz, E., Anzi, S., Swisa, A., Condiotti, R., Granit, R. Z., Nevo, Y., et al. (2016) · Nature Medicine · doi:10.1038/nm.4054 · Cited by 351 · see citing works
Role of immune cells in the removal of deleterious senescent cells
Kale, A., Sharma, A., Stolzing, A., Desprez, P.-Y., & Campisi, J. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-00187-9 · Cited by 351 · see citing works
Self-citationNKG2D ligands mediate immunosurveillance of senescent cells
Sagiv, A., Burton, D. G. A., Moshayev, Z., Vadai, E., Wensveen, F., Ben-Dor, S., Golani, O., Polic, B., & Krizhanovsky, V. (2016) · Aging · doi:10.18632/aging.100897 · Cited by 345 · see citing works
Wu, J. D., Higgins, L. M., Steinle, A., Cosman, D. J., Haugk, K. H., & Plymate, S. R. (2004) · Journal of Clinical Investigation · doi:10.1172/jci22206 · Cited by 331 · see citing works
Self-citationCoppé, J.-P., Patil, C. K., Rodier, F., Sun, Y., Muñoz, D. P., Goldstein, J., Nelson, P. S., Desprez, P.-Y., & Campisi, J. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060301 · Cited by 302 · cited 21× · see citing works
“Consistent with ATM-dependent upregulation of SASP factors (52) and NKG2D-Ls (Figure 2E), ATM-deficient XRA SnCs failed to repress NKG2D expression (Figure 8B).”
InfluentialSelf-citationEffect of Cytotoxic Chemotherapy on Markers of Molecular Age in Patients With Breast Cancer
Sanoff, H. K., Deal, A. M., Krishnamurthy, J., Torrice, C., Dillon, P., Sorrentino, J., Ibrahim, J. G., Jolly, T. A., Williams, G., Carey, L. A., et al. (2014) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/dju057 · Cited by 283 · see citing works
Identification of senescent cell surface targetable protein DPP4
Kim, K. M., Noh, J. H., Bodogai, M., Martindale, J. L., Yang, X., Indig, F. E., Basu, S. K., Ohnuma, K., Morimoto, C., Johnson, P. F., et al. (2017) · Genes & Development · doi:10.1101/gad.302570.117 · Cited by 270 · see citing works
A shed NKG2D ligand that promotes natural killer cell activation and tumor rejection
Deng, W., Gowen, B. G., Zhang, L., Wang, L., Lau, S., Iannello, A., Xu, J., Roviš, T. L., Xiong, N., & Raulet, D. H. (2015) · Science · doi:10.1126/science.1258867 · Cited by 256 · see citing works
Self-citationCellular senescence in vivo: Its relevance in ageing and cardiovascular disease
Erusalimsky, J. D., & Kurz, D. J. (2005) · Experimental Gerontology · doi:10.1016/j.exger.2005.04.010 · Cited by 252 · see citing works
Systemic NKG2D Down-Regulation Impairs NK and CD8 T Cell Responses In Vivo
Wiemann, K., Mittrücker, H., Feger, U., Welte, S. A., Yokoyama, W. M., Spies, T. A., Rammensee, H., & Steinle, A. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.2.720 · Cited by 240 · see citing works
Effect of training-sample size and classification difficulty on the accuracy of genomic predictors
Popovici, V. C., Chen, W., Gallas, B. D., Hatzis, C., Shi, W., Samuelson, F. W., Nikolsky, Y., Tsyganova, M., Ishkin, A., Nikolskaya, T., et al. (2010) · Breast Cancer Research · doi:10.1186/bcr2468 · Cited by 224 · see citing works
Iwamoto, T., Bianchini, G., Booser, D. J., Qi, Y., Coutant, C., Shiang, C. Y., Santarpia, L., Matsuoka, J., Hortobágyi, G. N., Symmans, W. F., et al. (2010) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djq524 · Cited by 220 · see citing works
Marty, B., Maire, V., Gravier, E., Rigaill, G. J., Vincent‐Salomon, A., Käppler, M., Lebigot, I., Djelti, F., Tourdès, A., Gestraud, P., et al. (2008) · Breast Cancer Research · doi:10.1186/bcr2204 · Cited by 216 · see citing works
Strategies targeting cellular senescence
Ovadya, Y., & Krizhanovsky, V. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95149 · Cited by 200 · see citing works
Senescent cells: a therapeutic target for cardiovascular disease
Childs, B. G., Li, H., & van Deursen, J. M. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95146 · Cited by 192 · see citing works
Chitadze, G., Lettau, M., Bhat, J., Wesch, D., Steinle, A., Furst, D. E., Mytilineos, J., Kalthoff, H., Janßen, O., Oberg, H., et al. (2013) · International Journal of Cancer · doi:10.1002/ijc.28174 · Cited by 189 · see citing works
Multifactorial Approach to Predicting Resistance to Anthracyclines
Desmedt, C., Leo, A. D., de Azambuja, E., Larsimont, D., Haibe‐Kains, B., Selleslags, J., Delaloge, S., Duhem, C., Kains, J.-P., Carly, B., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.31.2231 · Cited by 181 · see citing works
Crane, C. A., Austgen, K., Haberthur, K., Hofmann, C., Moyes, K. W., Avanesyan, L., Fong, L. H., Campbell, M. J., Cooper, S., Oakes, S. A., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1413933111 · Cited by 173 · see citing works
Bertheau, P., Turpin, E., Rickman, D. S., Espié, M., de Reyniès, A., Feugeas, J., Plassa, L., Soliman, H. R., Varna, M., de Roquancourt, A., et al. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040090 · Cited by 173 · see citing works
Le, O. N. L., Rodier, F., Fontaine, F., Coppe, J., Campisi, J., DeGregori, J., Laverdière, C., Kokta, V., Haddad, E., & Beauséjour, C. M. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00567.x · Cited by 168 · see citing works
Self-citationDiekman, B. O., Sessions, G. A., Collins, J. A., Knecht, A. K., Strum, S. L., Mitin, N. K., Carlson, C. S., Loeser, R. F., & Sharpless, N. E. (2018) · Aging Cell · doi:10.1111/acel.12771 · Cited by 158 · see citing works
The Fountain of Youth by Targeting Senescent Cells?
de Keizer, P. L. J. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2016.11.006 · Cited by 127 · see citing works
Soluble ULBP suppresses natural killer cell activity via down-regulating NKG2D expression
Song, H., Kim, J.-K., Cosman, D. J., & Choi, I. (2006) · Cellular Immunology · doi:10.1016/j.cellimm.2006.03.002 · Cited by 125 · see citing works
Perturbation of NK cell peripheral homeostasis accelerates prostate carcinoma metastasis
Liu, G., Lu, S., Wang, X., Page, S. T., Higano, C. S., Plymate, S. R., Greenberg, N. M., Sun, S., Li, Z., & Wu, J. D. (2013) · Journal of Clinical Investigation · doi:10.1172/jci69369 · Cited by 119 · see citing works
Self-citationOncogene-induced Cellular Senescence
Chandeck, C., & Mooi, W. J. (2010) · Advances in Anatomic Pathology · doi:10.1097/pap.0b013e3181c66f4e · Cited by 115 · see citing works
Beyond Tumor Suppression: Senescence in Cancer Stemness and Tumor Dormancy
Triana-Martínez, F., Loza, M. I., & Domínguez, E. (2020) · Cells · doi:10.3390/cells9020346 · Cited by 96 · see citing works
Desmedt, C., Giobbie‐Hurder, A., Neven, P., Paridaens, R., Christiaens, M., Smeets, A., Lallemand, F., Haibe‐Kains, B., Viale, G., Gelber, R. D., et al. (2009) · BMC Medical Genomics · doi:10.1186/1755-8794-2-40 · Cited by 81 · see citing works
Čížková, M., Cizeron-Clairac, G., Vacher, S., Susini, A., Andrieu, C., Lidereau, R., & Bièche, I. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015647 · Cited by 75 · see citing works
Irradiation induces glioblastoma cell senescence and senescence-associated secretory phenotype
Jeon, H.-Y., Kim, J.-K., Ham, S. W., Oh, S.-Y., Kim, J., Park, J.-B., Lee, J.-Y., Kim, S.-C., & Kim, H. (2016) · Tumor Biology · doi:10.1007/s13277-015-4439-2 · Cited by 73 · see citing works
NKG2D Ligand Shedding in Response to Stress: Role of ADAM10
Zingoni, A., Vulpis, E., Loconte, L., & Santoni, A. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00447 · Cited by 66 · see citing works
Senescence as an Amyloid Cascade: The Amyloid Senescence Hypothesis
Walton, C. C., Begelman, D. V., Nguyen, W., & Andersen, J. K. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00129 · Cited by 61 · see citing works
Klöß, S., Chambron, N., Gardlowski, T., Arseniev, L., Koch, J., Esser, R., Glienke, W., Seitz, O., & Koehl, U. (2015) · OncoImmunology · doi:10.1080/2162402x.2015.1055993 · Cited by 50 · see citing works
Raju, S., Kretzmer, L. Z., Koues, O. I., Payton, J. E., Oltz, E. M., Cashen, A. F., Polić, B., Schreiber, R. D., Shaw, A. S., & Markiewicz, M. A. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1501982 · Cited by 24 · see citing works
Jun, J.-I., & Lau, L. F. (2010) · Nature Cell Biology · doi:10.1038/ncb1210-1249 · Cited by 17 · see citing works
NKG2D ligands mediate immunosurveillance of senescent cells. Aging-US
Sagiv, A., Burton, D., Moshayev, Z., Wensveen, F. M., Ben‐Dor, S., Golani, O., Polić, B., & Krizhanovsky, V. (2016) · Aging-us · Cited by 8 · see citing works
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Research works printed but not linked: 1
- Coppé J-P. Aging and Cancer: Cell Non-Autonomous Effects of Senescent Fibroblasts on Tissue Microenvironment [dissertation]. Berkeley, California, USA: University of California, Berkeley; 2007.
Cited by
Sorted by citations
Exploiting senescence for the treatment of cancer
Wang, L., Lankhorst, L., & Bernards, R. (2022) · Nature Reviews Cancer · doi:10.1038/s41568-022-00450-9 · Cited by 867 · see citing works
Role of immune cells in the removal of deleterious senescent cells
Kale, A., Sharma, A., Stolzing, A., Desprez, P.-Y., & Campisi, J. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-00187-9 · Cited by 351 · see citing works
Self-citationInterconnections between Inflammageing and Immunosenescence during Ageing
Teissier, T., Boulanger, É., & Cox, L. S. (2022) · Cells · doi:10.3390/cells11030359 · Cited by 310 · see citing works
Mechanisms driving the immunoregulatory function of cancer cells
van Weverwijk, A., & de Visser, K. E. (2023) · Nature reviews. Cancer · doi:10.1038/s41568-022-00544-4 · Cited by 279 · see citing works
Senescence and Cancer: A Review of Clinical Implications of Senescence and Senotherapies
Wyld, L., Bellantuono, I., Tchkonia, T., Morgan, J., Turner, O., Foss, F., George, J., Danson, S., & Kirkland, J. L. (2020) · Cancers · doi:10.3390/cancers12082134 · Cited by 235 · see citing works
“Senescence is also an important mechanism of efficacy in the treatment of breast cancer with PARP inhibitors [59] and many typical chemotherapy agents used to treat breast cancer, such as epirubicin and cyclophosphamide [60].”
BackgroundAging of the Immune System: Focus on Natural Killer Cells Phenotype and Functions
Brauning, A., Rae, M. J., Zhu, G., Fulton, E. C., Admasu, T. D., Stolzing, A., & Sharma, A. (2022) · Cells · doi:10.3390/cells11061017 · Cited by 221 · see citing works
Aging immunity may exacerbate COVID-19
Akbar, A. N., & Gilroy, D. W. (2020) · Science · doi:10.1126/science.abb0762 · Cited by 209 · see citing works
NKG2D-CAR T cells eliminate senescent cells in aged mice and nonhuman primates
Yang, D., Sun, B., Li, S., Wei, W., Liu, X., Cui, X., Zhang, X., Liu, N., Yan, L., Deng, Y., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.add1951 · Cited by 214 · see citing works
Bone Aging, Cellular Senescence, and Osteoporosis
Pignolo, R. J., Law, S. F., & Chandra, A. (2021) · JBMR Plus · doi:10.1002/jbm4.10488 · Cited by 206 · see citing works
Senescence in osteoarthritis: from mechanism to potential treatment
Liu, Y., Zhang, Z., Li, T., Xu, H., & Zhang, H. (2022) · Arthritis Research & Therapy · doi:10.1186/s13075-022-02859-x · Cited by 206 · see citing works
Reducing Senescent Cell Burden in Aging and Disease
Pignolo, R. J., Passos, J. F., Khosla, S., Tchkonia, T., & Kirkland, J. L. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.03.005 · Cited by 177 · see citing works
The Skin Microbiome: Current Landscape and Future Opportunities
Smythe, P., & Wilkinson, H. N. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043950 · Cited by 207 · see citing works
Saleh, T., Carpenter, V. J., Tyutyunyk‐Massey, L., Murray, G., Leverson, J. D., Souers, A. J., Alotaibi, M. R., Faber, A. C., Reed, J., Harada, H., et al. (2020) · Molecular Oncology · doi:10.1002/1878-0261.12761 · Cited by 190 · see citing works
Senescence as a therapeutic target in cancer and age-related diseases
McHugh, D., Durán, I., & Gil, J. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-01074-4 · Cited by 199 · see citing works
Discovering dominant tumor immune archetypes in a pan-cancer census
Combes, A. J., Samad, B., Tsui, J. L., Chew, N. W., Yan, P., Reeder, G. C., Kushnoor, D., Shen, A. S., Davidson, B. R., Barczak, A. J., et al. (2021) · Cell · doi:10.1016/j.cell.2021.12.004 · Cited by 163 · see citing works
Why Senescent Cells Are Resistant to Apoptosis: An Insight for Senolytic Development
Hu, L., Li, H., Zi, M., Li, W., Liu, J., Yang, Y., Zhou, D., Kong, Q., Zhang, Y., & He, Y. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.822816 · Cited by 167 · see citing works
Senescence and the tumor-immune landscape: Implications for cancer immunotherapy
Chibaya, L., Snyder, J. T., & Ruscetti, M. A. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.02.005 · Cited by 138 · see citing works
Upregulation of PD-L1 in Senescence and Aging
Onorati, A., Havas, A. P., Lin, B., Rajagopal, J., Sen, P., Adams, P. D., & Dou, Z. (2022) · Molecular and Cellular Biology · doi:10.1128/mcb.00171-22 · Cited by 131 · see citing works
Targeting Senescent Cells for a Healthier Aging: Challenges and Opportunities
Song, S., Tchkonia, T., Jiang, J., Kirkland, J. L., & Sun, Y. (2020) · Advanced Science · doi:10.1002/advs.202002611 · Cited by 129 · see citing works
Self-citationSenolytics 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
The efficacy of chemotherapy is limited by intratumoral senescent cells expressing PD-L2
Chaib, S., López-Domínguez, J. A., Lalinde-Gutiérrez, M., Prats, N., Marin, I., Boix, O., García-Garijo, A., Meyer, K., Muñoz, M. I., Aguilera, M., et al. (2024) · Nature Cancer · doi:10.1038/s43018-023-00712-x · Cited by 114 · see citing works
Targeting senescence as an anticancer therapy
Bousset, L., & Gil, J. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13312 · Cited by 108 · see citing works
Biological functions of therapy-induced senescence in cancer
Fitsiou, E., Soto-Gamez, A., & Demaria, M. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.03.021 · Cited by 101 · see citing works
Cellular senescence as a potential mediator of COVID‐19 severity in the elderly
Nehme, J., Borghesan, M., Mackedenski, S., Bird, T. G., & Demaria, M. (2020) · Aging Cell · doi:10.1111/acel.13237 · Cited by 94 · see citing works
Liu, H., Zhao, H., & Sun, Y. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.11.004 · Cited by 96 · see citing works
Self-citationBeyond Tumor Suppression: Senescence in Cancer Stemness and Tumor Dormancy
Triana-Martínez, F., Loza, M. I., & Domínguez, E. (2020) · Cells · doi:10.3390/cells9020346 · Cited by 96 · see citing works
The role of senescent T cells in immunopathology
Covre, L. P., De Maeyer, R. P. H., Gomes, D. C. O., & Akbar, A. N. (2020) · Aging Cell · doi:10.1111/acel.13272 · Cited by 93 · see citing works
Targeting 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
Dissecting primary and secondary senescence to enable new senotherapeutic strategies
Admasu, T. D., Rae, M. J., & Stolzing, A. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101412 · Cited by 92 · see citing works
Cellular senescence in cancer: clinical detection and prognostic implications
Domen, A., Deben, C., Verswyvel, J., Flieswasser, T., Prenen, H., Peeters, M., Lardon, F., & Wouters, A. (2022) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-022-02555-3 · Cited by 94 · see citing works
Shahbandi, A., Chiu, F.-Y., Ungerleider, N., Kvadas, R. M., Mheidly, Z., Sun, M. J. S., Tian, D., Waizman, D. A., Anderson, A. Y., Machado, H. L., et al. (2022) · Nature Cancer · doi:10.1038/s43018-022-00466-y · Cited by 85 · see citing works
Jia, Y., Han, L., Ramage, C. L., Wang, Z., Weng, C. C. Y., Yang, L., Colla, S., Ma, H., Zhang, W., Andreeff, M., et al. (2023) · Haematologica · doi:10.3324/haematol.2022.281915 · Cited by 76 · see citing works
Salminen, A. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101280 · Cited by 76 · see citing works
The Emergence of Senescent Surface Biomarkers as Senotherapeutic Targets
Rossi, M. S., & Abdelmohsen, K. (2021) · Cells · doi:10.3390/cells10071740 · Cited by 73 · see citing works
Cellular Plasticity: A Route to Senescence Exit and Tumorigenesis
Blander, H. D., Morel, A., Senaratne, A. P., Ouzounova, M., & Puisieux, A. (2021) · Cancers · doi:10.3390/cancers13184561 · Cited by 74 · see citing works
The 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
Cellular Senescence: Mechanisms, Morphology, and Mouse Models
Beck, J. A., Horikawa, I., & Harris, C. C. (2020) · Veterinary Pathology · doi:10.1177/0300985820943841 · Cited by 72 · see citing works
Time-dependent replicative senescence vs. disturbed flow-induced pre-mature aging in atherosclerosis
Dominic, A., Banerjee, P., Hamilton, D. J., Le, N., & Abe, J. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101614 · Cited by 71 · see citing works
Targeting tumor cell senescence and polyploidy as potential therapeutic strategies
Saleh, T., Carpenter, V. J., Bloukh, S., & Gewirtz, D. A. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.12.010 · Cited by 70 · see citing works
Cellular senescence in lymphoid organs and immunosenescence
Budamagunta, V., Foster, T. C., & Zhou, D. (2021) · Aging · doi:10.18632/aging.203405 · Cited by 68 · see citing works
NKG2D Ligand Shedding in Response to Stress: Role of ADAM10
Zingoni, A., Vulpis, E., Loconte, L., & Santoni, A. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00447 · Cited by 66 · see citing works
Liu, Y., Lomeli, I., & Kron, S. J. (2024) · Cells · doi:10.3390/cells13151281 · Cited by 72 · see citing works
Exercise Counters the Age-Related Accumulation of Senescent Cells
Zhang, X., Englund, D. A., Aversa, Z., Jachim, S. K., White, T. A., & LeBrasseur, N. K. (2022) · Exercise and Sport Sciences Reviews · doi:10.1249/jes.0000000000000302 · Cited by 63 · see citing works
Senescence as an Amyloid Cascade: The Amyloid Senescence Hypothesis
Walton, C. C., Begelman, D. V., Nguyen, W., & Andersen, J. K. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00129 · Cited by 61 · 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
Microglial response to aging and neuroinflammation in the development of neurodegenerative diseases
Han, T., Xu, Y., Sun, L., Hashimoto, M., & Wei, J. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.385845 · Cited by 60 · see citing works
Aging and homeostasis of the hypodermis in the age-related deterioration of skin function
Liu, M., Lu, F., & Feng, J. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06818-z · Cited by 61 · see citing works
Senescence-Associated Secretory Phenotype as a Hinge Between Cardiovascular Diseases and Cancer
Banerjee, P., Kotla, S., Velatooru, L. R., Abe, R. J., Olmsted‐Davis, E. A., Cooke, J. P., Schadler, K., Deswal, A. M., Herrmann, J., Lin, S. H., et al. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.763930 · Cited by 54 · see citing works
Senescence-associated hyper-activation to inflammatory stimuli in vitro
Budamagunta, V., Manohar‐Sindhu, S., Yang, Y., He, Y., Traktuev, D. O., Foster, T. C., & Zhou, D. (2021) · Aging · doi:10.18632/aging.203396 · Cited by 54 · see citing works
Luo, J., Sun, T., Liu, Z., Liu, Y., Liu, J., Wang, S., Shi, X., & Zhou, H. (2025) · International Journal of Oral Science · doi:10.1038/s41368-025-00380-w · Cited by 56 · see citing works
Senescent 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
The senescence-associated secretory phenotype: Fueling a wound that never heals
Pulido, T., Velarde, M. C., & Alimirah, F. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111561 · Cited by 51 · see citing works
Senescence-induced immune remodeling facilitates metastatic adrenal cancer in a sex-dimorphic manner
Warde, K. M., Smith, L., Liu, L., Stubben, C., Lohman, B. K., Willett, P. W., Ammer, J. L., Castaneda-Hernandez, G., Imodoye, S. O., Zhang, C., et al. (2023) · Nature Aging · doi:10.1038/s43587-023-00420-2 · Cited by 47 · see citing works
Cell senescence in cardiometabolic diseases
Grootaert, M. O. J. (2024) · npj Aging · doi:10.1038/s41514-024-00170-4 · Cited by 54 · see citing works
An ERK5-NRF2 Axis Mediates Senescence-Associated Stemness and Atherosclerosis
Abe, J., Imanishi, M., Li, S., Zhang, A., Ko, K. A., Samanthapudi, V. S. K., Lee, L.-L., Paniagua-Bojorges, A., Gi, Y. J., Hobbs, B. P., et al. (2023) · Circulation Research · doi:10.1161/circresaha.122.322017 · Cited by 46 · see citing works
Deconstructing tumor heterogeneity: the stromal perspective
Vickman, R. E., Faget, D. V., Beachy, P. A., Beebe, D. J., Bhowmick, N. A., Cukierman, E., Deng, W.-M., Granneman, J. G., Hildesheim, J., Kalluri, R., et al. (2020) · Oncotarget · doi:10.18632/oncotarget.27736 · Cited by 43 · see citing works
Self-citationSaleh, T., & Gewirtz, D. A. (2022) · British Journal of Cancer · doi:10.1038/s41416-022-01787-6 · Cited by 42 · see citing works
Bai, Z., Yang, P., Yu, F., Li, Z., Yao, Z., Martinez, J., Li, M., & Xu, H. (2022) · Cell Death & Disease · doi:10.1038/s41419-022-04562-w · Cited by 43 · see citing works
“DDR is critical in inducing SNCs to up regulate NKG2D ligands, which enables NK cells to recognize and clear SNCs in a timely manner [37].”
BackgroundThe Role of Ageing and Parenchymal Senescence on Macrophage Function and Fibrosis
Campbell, R., Docherty, M.-H., Ferenbach, D. A., & Mylonas, K. J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.700790 · Cited by 40 · see citing works
A guide to senolytic intervention in neurodegenerative disease
Lee, S., Wang, E. Y., Steinberg, A. B., Walton, C. C., Chinta, S. J., & Andersen, J. K. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111585 · Cited by 43 · see citing works
Cellular senescence signaling in cancer: A novel therapeutic target to combat human malignancies
Fakhri, S., Moradi, S. Z., DeLiberto, L. K., & Bishayee, A. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.114989 · Cited by 38 · see citing works
Harnessing Natural Killer Cells in Non-Small Cell Lung Cancer
Russell, É., Conroy, M. J., & Barr, M. P. (2022) · Cells · doi:10.3390/cells11040605 · Cited by 37 · see citing works
Insights into the role of senescence in tumor dormancy: mechanisms and applications
DeLuca, V. J., & Saleh, T. (2023) · Cancer and Metastasis Reviews · doi:10.1007/s10555-023-10082-6 · Cited by 36 · see citing works
Targeting cellular senescence in cancer by plant secondary metabolites: A systematic review
Fakhri, S., Moradi, S. Z., Ash-Rafzadeh, A., & Bishayee, A. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105961 · Cited by 37 · see citing works
Enhancing immunity during ageing by targeting interactions within the tissue environment
Bracken, O. V., Maeyer, R. P. H. D., & Akbar, A. N. (2025) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-01126-9 · Cited by 40 · see citing works
Cellular senescence offers distinct immunological vulnerabilities in cancer
Zhou, L., Ma, B., & Ruscetti, M. A. (2024) · Trends in cancer · doi:10.1016/j.trecan.2024.11.010 · Cited by 36 · see citing works
Shachar, S. S., Deal, A. M., Reeder-Hayes, K. E., Nyrop, K. A., Mitin, N., Anders, C. K., Carey, L., Dees, E. C., Jolly, T. A., Kimmick, G. G., et al. (2020) · JNCI Cancer Spectrum · doi:10.1093/jncics/pkaa082 · Cited by 33 · see citing works
Chaturvedi, P., George, V., Shrestha, N., Wang, M., Dee, M. J., Zhu, X., Liu, B., Egan, J. O., D’Eramo, F., Spanoudis, C. M., et al. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.01.025 · Cited by 33 · see citing works
A nutrigeroscience approach: Dietary macronutrients and cellular senescence
Calubag, M. F., Robbins, P. D., & Lamming, D. W. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.07.025 · Cited by 32 · see citing works
Almasabi, S., Ahmed, A. U., Boyd, R. L., & Williams, B. R. G. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.638558 · Cited by 30 · see citing works
Cellular Senescence in Hepatocellular Carcinoma: The Passenger or the Driver?
Cai, X., Guillot, A., & Liu, H. (2022) · Cells · doi:10.3390/cells12010132 · Cited by 30 · see citing works
Reliable Hallmarks and Biomarkers of Senescent Lymphocytes
Сергеевна, М. Ю., Tereshchenko, V., Bogdanova, D. A., & Александрович, Р. С. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242115653 · Cited by 28 · see citing works
Escriche‐Navarro, B., Garrido, E. M. N., Sancenón, F., García‐Fernández, A., & Martínez‐Máñez, R. (2024) · Acta Biomaterialia · doi:10.1016/j.actbio.2024.01.002 · Cited by 27 · 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
Senotherapies: A novel strategy for synergistic anti-tumor therapy
Qi, X., Li, J., & Cao, J. (2022) · Drug Discovery Today · doi:10.1016/j.drudis.2022.103365 · Cited by 25 · see citing works
Farhana, A., Alsrhani, A., Khan, Y. S., & Rasheed, Z. (2023) · Cancers · doi:10.3390/cancers15153836 · Cited by 25 · see citing works
Impact of senolytic treatment on immunity, aging, and disease
Lorenzo, E. C., Torrance, B. L., & Haynes, L. (2023) · Frontiers in Aging · doi:10.3389/fragi.2023.1161799 · Cited by 27 · see citing works
Targeting immunosenescence for improved tumor immunotherapy
Liu, Z., Zuo, L., Zhou, Z., Liu, S., Ba, Y., Zuo, A., Ren, Y., Zhang, C., Chen, Y., Ma, H., et al. (2024) · MedComm · doi:10.1002/mco2.777 · Cited by 24 · see citing works
Role of low-dose radiation in senescence and aging: A beneficial perspective
Xu, J., Liu, D., Zhao, D., Jiang, X. M., Meng, X., Jiang, L., Meina, Y., Zhang, L., & Jiang, H. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120644 · Cited by 25 · see citing works
Fabbri, F., Salvi, S., & Bravaccini, S. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.10.015 · Cited by 24 · see citing works
Therapy-Induced Senescence: Novel Approaches for Markers Identification
Pacifico, F., Magni, F., Leonardi, A., & Crescenzi, E. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25158448 · Cited by 25 · see citing works
Senescence and Type 2 Diabetic Cardiomyopathy: How Young Can You Die of Old Age?
Henson, S. M., & Aksentijević, D. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.716517 · Cited by 23 · see citing works
The Dynamic Process and Its Dual Effects on Tumors of Therapy-Induced Senescence
Liao, C., Xiao, Y., & Liu, L. (2020) · Cancer Management and Research · doi:10.2147/cmar.s285083 · Cited by 22 · see citing works
Saleh, T., Khasawneh, A. I., Himsawi, N. M., Abu-Raideh, J. A., Ejeilat, V., Elshazly, A. M., & Gewirtz, D. A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232415512 · Cited by 21 · see citing works
Qamsari, E. S., & Stewart, D. J. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1403669 · Cited by 21 · see citing works
Therapy-induced senescence is finally escapable, what is next?
Saleh, T. (2024) · Cell Cycle · doi:10.1080/15384101.2024.2364579 · Cited by 21 · 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
Hernández‐Mercado, E., Prieto‐Chávez, J. L., Arriaga‐Pizano, L., Hernández-Gutiérrez, S., Mendlovic, F., Königsberg, M., & López‐Díazguerrero, N. E. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910215 · Cited by 19 · see citing works
Tsuji, K., Kida, Y., Koshikawa, N., Yamamoto, S., Shinozaki, Y., Watanabe, T., Lin, J. C., Nagase, H., & Takenaga, K. (2022) · Cancer Science · doi:10.1111/cas.15290 · Cited by 19 · see citing works
Sobeai, H. M. A., Alohaydib, M. H., Alhoshani, A., Alhazzani, K., Almutairi, M. M., Saleh, T., Gewirtz, D. A., & Alotiabi, M. R. (2021) · Saudi Pharmaceutical Journal · doi:10.1016/j.jsps.2021.12.004 · Cited by 18 · 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
Massa, D., Tosi, A., Rosato, A., Guarneri, V., & Dieci, M. (2022) · Cancers · doi:10.3390/cancers14194885 · Cited by 9 · see citing works
Metabolic regulation of endothelial senescence
Le, N.-T. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1232681 · Cited by 15 · see citing works
Can 3D bioprinting solve the mystery of senescence in cancer therapy?
Shboul, S. A., DeLuca, V. J., Dweiri, Y. M., & Saleh, T. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101732 · Cited by 15 · see citing works
Senescence Promotes the Recovery of Stemness among Cancer Cells via Reprograming
Wang, D., & Liu, L. (2024) · Biomolecules · doi:10.3390/biom14030288 · Cited by 14 · see citing works
Role of Senescence in Tumorigenesis and Anticancer Therapy
Stoczyńska-Fidelus, E., Węgierska, M., Kierasińska, A., Ciunowicz, D., & Rieske, P. (2022) · Journal of Oncology · doi:10.1155/2022/5969536 · Cited by 15 · see citing works
Huang, R., Wang, H., Hong, J., Wang, Z., Wu, J., Huang, O., He, J., Chen, W., Li, Y., Chen, X., et al. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1191910 · Cited by 13 · see citing works
Self-citationAbu-Humaidan, A. H. A., Ismail, M. A., Ahmad, F. M., Shboul, S. A., Barham, R., Tadros, J. S., Alhesa, A., El‐Sadoni, M., Alotaibi, M. R., Ababneh, N. A., et al. (2024) · Immunology and Cell Biology · doi:10.1111/imcb.12727 · Cited by 13 · see citing works
Senescence-related genes as prognostic indicators in breast cancer survival
Ungvari, Z. I., Ungvari, A., Fekete, M., Kiss, C., & Győrffy, B. (2024) · GeroScience · doi:10.1007/s11357-024-01384-w · Cited by 14 · see citing works
Nutritional Niches of Cancer Therapy-Induced Senescent Cells
Llop‐Hernández, À., Verdura, S., Cuyàs, E., & Menéndez, J. A. (2022) · Nutrients · doi:10.3390/nu14173636 · Cited by 13 · see citing works
- Authors
- Muñoz, D. P., Yannone, S. M., Daemen, A., Sun, Y., Vakar-Lopez, F., Kawahara, M., Freund, A. M., Rodier, F., Wu, J. D., Desprez, P.-Y., Raulet, D. H., Nelson, P. S., van ’t Veer, L. J., Campisi, J., & Coppé, J.-P.
- Affiliations
- University of California, San Francisco (US)
- Lawrence Berkeley National Laboratory (US)
- Fred Hutch Cancer Center (US)
- Department of Pathology, University of Washington, Seattle, Washington, USA.
- Buck Institute for Research on Aging (US)
- Lawrence Berkeley National Laboratory, Life Sciences Division, Berkeley, California, USA.
- University of Washington (US)
- University of California, Berkeley (US)
- Helen Diller Family Comprehensive Cancer Center, Department of Laboratory Medicine, UCSF, San Francisco, California, USA.
- Corresponding author
- Coppé, Jean-Philippe
- ORCID
- Venue
- JCI Insight
- Published
- 2019-07-25
- Volume
- 4
- Issue
- 14
- ISSN
- 2379-3708 (ISSN-L)
- PMC
- PMC6675550
- OpenAlex
- W2952749575
- Cited by
- 162
- References
- 92
- Citations by year
- 2026: 18 · 2025: 18 · 2024: 25 · 2023: 21 · 2022: 30 · 2021: 26 · 2020: 23 · 2019: 1
- FWCI
- 13.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- JCI Insight (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute on Aging (R56AG009909, R37AG009909, P01AG017242)
- National Cancer Institute (R01CA093678, R01CA204021, R01CA165573, P50CA097186)
- National Institute of Allergy and Infectious Diseases (R01AI113041)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- cellular senescence, senescent cells, immune evasion, NKG2D, natural killer cells, matrix metalloproteinases, immune surveillance, immunoediting, chemoresistance, aging, prostate cancer, breast cancer, Ras-induced senescence, p16INK4a, benign nevi, tumor microenvironment
- MeSH terms
- Aging, Animals, Antineoplastic Agents, Biopsy, Breast, Breast Neoplasms, DNA Damage, Female, Humans, Immunologic Surveillance, Male, Metalloendopeptidases, Prostate, Prostatic Neoplasms, Gene Expression Regulation, Neoplastic, Cellular Senescence, Drug Resistance, Neoplasm, Tumor Escape, Cyclin-Dependent Kinase Inhibitor p16, Gene Expression Profiling, Cell Line, Tumor, Tissue Array Analysis, Mice, NK Cell Lectin-Like Receptor Subfamily K, Tumor Microenvironment, Datasets as Topic
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