p21 produces a bioactive secretome that places stressed cells under immunosurveillance
Open accessAbstract
The clock is ticking for senescent cells: Senescent cells promote their own recognition and removal through the immune system by generating a bioactive secretome called the senescence-associated secretory phenotype (SASP). Sturmlechner et al . report that the cell cycle regulator p21 directs an early form of the SASP, which they call the p21-activated secretory phenotype (PASP) (see the Perspective by Reen and Gil). As part of the PASP, the chemokine CXCL14 attracts macrophages, which monitor stressed cells expressing elevated p21. If stressed cells recuperate and p21 levels return to normal within 4 days, then macrophages disengage from their targets. Otherwise, macrophages recruit cytotoxic T cells that facilitate target cell removal. Other cell cycle regulators such as p16 can induce many factors overlapping with the PASP, but p21 uniquely drives this CXCL14-mediated “timer” mechanism of senescent cell immunosurveillance. —STS
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Overexpression of p21 or p16 in mouse embryonic fibroblasts led to distinct secretome profiles, showing only partial overlap.
“This is in line with previous studies in which overexpression of p21 or p16 in mouse embryonic fibroblasts led to distinct secretome profiles (Sturmlechner et al, 2021), showing only partial overlap (Fig. EV9A,B).”
From Distinct senotypes in p16- and p21-positive cells across human and mouse aging tissues (2025) · cites this paper as Sturmlechner et al, 2021
In “p21 enforces immunosurveillance through the chemokine CXCL14” (page not specified), the paper compares p21- and p16-overexpressing mouse embryonic fibroblasts and reports differences in their secretomes. But 183 of the 197 p16-associated factors overlap with the p21-associated secretome, which the paper describes as having a high degree of similarity; “only partial overlap” overstates the difference. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn a different mouse model of liver cancer, sustained expression of p21 induced a senescence programme with a peculiar secretory phenotype including CXCL14 and IGFBP3, which contributed to macrophage and lymphocyte recruitment to the tumour site, thus activating immunosurveillance mechanisms.
“In a different mouse model of liver cancer, sustained expression of p21 was found to induce a senescence programme with a peculiar secretory phenotype including CXCL14 and IGFBP3, which contributed to macrophage and lymphocyte recruitment to the tumour site, thus activating immunosurveillance mechanisms 146 .”
From Senescence and cancer — role and therapeutic opportunities (2022) · cites this paper as [146]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredA recent study has demonstrated that p21 and p16 overexpression elicit distinct secretory phenotypes, with the p21-driven phenotype promoting immunosurveillance.
“Consistent with the functional diversity of these subpopulations, a recent study has demonstrated that p21 and p16 overexpression elicit distinct secretory phenotypes, with the p21-driven phenotype promoting immunosurveillance (Sturmlechner et al, 2021).”
From Distinct senotypes in p16- and p21-positive cells across human and mouse aging tissues (2025) · cites this paper as Sturmlechner et al, 2021
The tumour suppressor p53-p21 axis cell-autonomously controls the OIS response, but additionally mediates communication between senescent cells and immune cells, presumably via the SASP.
“The tumour suppressor p53-p21 axis cell- autonomously controls the OIS response, but additionally mediates communication between senescent cells and immune cells, presumably via the SASP 144-146 .”
From Senescence and cancer — role and therapeutic opportunities (2022) · cites this paper as [146]
A p21/Rb pathway produces a p21-activated secretory phenotype (PASP) that directs a CXCL14-mediated mechanism of senescent cell immunosurveillance.
“A p21/Rb pathway also produces a p21-activated secretory phenotype (PASP) that directs a CXCL14-mediated mechanism of senescent cell immunosurveillance (34).”
From Connecting aging biology and inflammation in the omics era (2022) · cites this paper as [34]
Senescence markers beyond p16 include p21, p19, uPAR, and GPNMB.
“Studies have begun to reveal the remarkable heterogeneity of cellular senescence in different tissues, highlighting the importance of cellular senescence markers beyond p16 – including Cdkn1a (p21) [7–10], Cdkn2d (p19) [11], uPAR [12], and glycoprotein non-metastatic melanoma protein B (GPNMB) [13] – and emphasizing the urgent need for a better understanding of senescent cell heterogeneity.”
From The heterogeneity of cellular senescence: insights at the single-cell level (2023) · cites this paper as [7]
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Disruption of CXC Motif Chemokine Ligand-14 in Mice Ameliorates Obesity-induced Insulin Resistance
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Cyclin B2 and p53 control proper timing of centrosome separation
Nam, H.-J., & van Deursen, J. (2014) · Nature Cell Biology · doi:10.1038/ncb2952 · Cited by 168 · cited 1× · see citing works
“L-KRAS mice were generated from KH2 ES (C57BL/6×129Sv) cells according to previously describedmethods (39) using amodified pBS31 vector.”
MethodChen, X., Mitsutake, N., LaPerle, K., Akeno, N., ZANZONICO, P. B., Longo, V. A., Mitsutake, S., Kimura, E. T., Geiger, H., Santos, E., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900343106 · Cited by 139 · cited 1× · see citing works
“Duplicate measures were averaged and cumulative cell number was calculated according to the following formula (70) Tx = Tx−1 * Nx / N0, where T is the cumulative cell number, x the passage number, Nx the counted cell number at passage x, and N0 the initially seeded cell number.”
MethodIRX1 hypomethylation promotes osteosarcoma metastasis via induction of CXCL14/NF-κB signaling
Lu, J., Song, G., Tang, Q., Zou, C., Han, F., Zhao, Z., Yong, B., Yin, J., Xu, H., Xie, X., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci78437 · Cited by 122 · see citing works
A Code of Mono-phosphorylation Modulates the Function of RB
Sanidas, I., Morris, R. T., Fella, K. A., Rumde, P. H., Boukhali, M., Tai, E. C., Ting, D. T., Lawrence, M. S., Haas, W., & Dyson, N. J. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.01.004 · Cited by 119 · cited 1× · see citing works
“However, hypophosphorylated Rb appears to be a collection of Rbmolecules that are monophosphorylated at one of 14 known phosphorylation sites, with each variant having a characteristic binding-partner profile and a distinctive transcriptional output (34).”
BackgroundHamada, M., Haeger, A., Jeganathan, K. B., van Ree, J. H., Malureanu, L. A., Wälde, S., Joseph, J., Kehlenbach, R. H., & van Deursen, J. M. (2011) · The Journal of Cell Biology · doi:10.1083/jcb.201102018 · Cited by 109 · cited 2× · see citing works
“The Myc-Flagtagged cDNA for mouse p21 was obtained from Origene (#MR227529) and subcloned into the lentiviral pTSIN-PGK-puro2 backbone (43, 67) or dox-inducible pTRIPZ-PKG-puro backbone (modified from GE Dharmacon) (68).”
MethodSelf-citationReversal of Hepatocyte Senescence After Continuous In Vivo Cell Proliferation
Wang, M., Chen, F., Li, J., Liu, C.-C., Zhang, H., Xia, Y., Yu, B., You, P., Xiang, D., Lu, L., et al. (2014) · Hepatology · doi:10.1002/hep.27094 · Cited by 103 · cited 1× · see citing works
“To determine the proportion of SA-b-Gal hepatocytes in adeno-Cre induced livers, 8-mm-thick cryosections were cut and stained similarly to described previously (69).”
MethodThe multifarious roles of the chemokine CXCL14 in cancer progression and immune responses
Westrich, J. A., Vermeer, D. W., Colbert, P. L., Spanos, W. C., & Pyeon, D. (2020) · Molecular Carcinogenesis · doi:10.1002/mc.23188 · Cited by 103 · cited 1× · see citing works
“The observation that low CXCL14 expression correlates with poor clinical outcome in various human cancers, including cervical, colorectal, endometrial, and head and neck cancers (38), underscores the relevance of such future efforts.”
BackgroundLiver-Specific pRB Loss Results in Ectopic Cell Cycle Entry and Aberrant Ploidy
Mayhew, C. N., Bosco, E. E., Fox, S. R., Okaya, T., Tarapore, P., Schwemberger, S. J., Babcock, G. F., Lentsch, A. B., Fukasawa, K., & Knudsen, E. S. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-4221 · Cited by 101 · cited 1× · see citing works
“PCR analysis of Rb exon 19 was performed as described before (65) using the following primers Rb18 (F) 5′-GGCGTGTGCATCAATG-3′ and Rb212 (R) 5′-GAAAGGAAAGTCAGGGACATTGGG-3′ generating 698 bp, 746 bp, and 260 bp products for the wild-type, unrecombined-floxed, and recombined-floxed alleles, respectively.”
MethodTRAIL mediates liver injury by the innate immune system in the bile duct–ligated mouse†
Kahraman, A., Barreyro, F. J., Bronk, S. F., Werneburg, N. W., Mott, J. L., Akazawa, Y., Masuoka, H. C., Howe, C. L., & Gores, G. J. (2008) · Hepatology · doi:10.1002/hep.22136 · Cited by 90 · cited 1× · see citing works
“To isolate Tom liver cells, livers of Ai14;L-KRAS or Ai14 control mice 8 days post-injection were perfused with collagenase as previously described (63, 64).”
MethodRole of Cyclin Kinase Inhibitor p21 in Systemic Autoimmunity
Santiago‐Raber, M., Lawson, B. R., Dummer, W., Barnhouse, M., Koundouris, S., Wilson, C. B., Kono, D. H., & Theofilopoulos, A. N. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.7.4067 · Cited by 83 · see citing works
Pleiotropic functions of the CXC-type chemokine CXCL14 in mammals
Hara, T., & Tanegashima, K. (2012) · The Journal of Biochemistry · doi:10.1093/jb/mvs030 · Cited by 79 · see citing works
Macrophages are the primary effector cells in IL-7-induced arthritis
Kim, S.-J., Chang, H. J., Volin, M. V., Umar, S., Raemdonck, K. V., Chevalier, A., Palasiewicz, K., Christman, J. W., Volkov, S., Arami, S., et al. (2019) · Cellular and Molecular Immunology · doi:10.1038/s41423-019-0235-z · Cited by 73 · cited 1× · see citing works
“Both these interleukins induce M1 macrophage differentiation (36, 37), a phenotypic change that we show coincides with the recruitment of cytotoxic T cells to p21-expressing hepatocytes.”
BackgroundAziz, K., Limzerwala, J. F., Sturmlechner, I., Hurley, E., Zhang, C., Jeganathan, K. B., Nelson, G. G., Bronk, S. F., Velasco, R. O. F., van Deursen, E.-J., et al. (2019) · Gastroenterology · doi:10.1053/j.gastro.2019.03.016 · Cited by 69 · cited 1× · see citing works
“To isolate Tom liver cells, livers of Ai14;L-KRAS or Ai14 control mice 8 days post-injection were perfused with collagenase as previously described (63, 64).”
MethodSelf-citationLawson, B. R., Baccalà, R., Song, J. J., Croft, M., Kono, D. H., & Theofilopoulos, A. N. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20031685 · Cited by 65 · see citing works
Purification of nanogram-range immunoprecipitated DNA in ChIP-seq application
Zhong, J., Ye, Z., Lenz, S. W., Clark, C. R., Bharucha, A. E., Farrugia, G., Robertson, K. D., Zhang, Z., Ördög, T., & Lee, J. (2017) · BMC Genomics · doi:10.1186/s12864-017-4371-5 · Cited by 56 · cited 3× · see citing works
“A total of 2×10(5) to 1×10(6) cells were fixed with 1% paraformaldehyde (PFA) for 10 min and then subjected to ChIP-seq as previously described using a rabbit anti-H3K27Ac antibody (Abcam, ab4729, Lot GR150367) (44).”
MethodInfluentialSelf-citationModulation of therapy-induced senescence by reactive lipid aldehydes
Flor, A. C., Doshi, A. P., & Kron, S. J. (2016) · Cell Death Discovery · doi:10.1038/cddiscovery.2016.45 · Cited by 40 · see citing works
Intensive RNAi with lentiviral vectors in mammalian cells
Miest, T. S., Saenz, D. T., Meehan, A. M., Llano, M., & Poeschla, E. M. (2008) · Methods · doi:10.1016/j.ymeth.2008.11.001 · Cited by 21 · see citing works
BubR1 alterations that reinforce mitotic surveillance act against aneuploidy and cancer
Weaver, R. L., Limzerwala, J. F., Naylor, R. M., Jeganathan, K. B., Baker, D. J., & van Deursen, J. M. (2016) · eLife · doi:10.7554/elife.16620 · Cited by 20 · cited 2× · see citing works
“The Myc-Flagtagged cDNA for mouse p21 was obtained from Origene (#MR227529) and subcloned into the lentiviral pTSIN-PGK-puro2 backbone (43, 67) or dox-inducible pTRIPZ-PKG-puro backbone (modified from GE Dharmacon) (68).”
MethodSelf-citation
Flagged first, then by citations
Cited by
Sorted by citations
The senescence-associated secretory phenotype and its physiological and pathological implications
Wang, B., Han, J., Elisseeff, J. H., & Demaria, M. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00727-x · Cited by 948 · see citing works
“Both p53–p21 and p16 directly regulate the SASP: p21 supports an early secretory phenotype that includes CXCL14 and IGFBP3, which puts stressed or senescent cells under immunosurveil-lance, and this process is mediated by Rb activation 75 .”
Senescence and cancer — role and therapeutic opportunities
Schmitt, C. A., Wang, B., & Demaria, M. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00668-4 · Cited by 794 · see citing works
Chronic inflammation and the hallmarks of aging
Baechle, J. J., Chen, N., Makhijani, P., Winer, S., Furman, D., & Winer, D. A. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101755 · Cited by 471 · see citing works
“For instance, p21-induced senescence induces a distinct SASP characterized by C-X-C motif chemokine 14 (CXCL14) expression, which puts stressed cells under immunosurveillance [352].”
BackgroundThe heterogeneity of cellular senescence: insights at the single-cell level
Cohn, R. L., Gasek, N. S., Kuchel, G. A., & Xu, M. (2023) · Trends in Cell Biology · doi:10.1016/j.tcb.2022.04.011 · Cited by 294 · see citing works
Senescent alveolar macrophages promote early-stage lung tumorigenesis
Prieto, L. I., Sturmlechner, I., Graves, S. I., Zhang, C., Goplen, N. P., Yi, E. S., Sun, J., Li, H., & Baker, D. J. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.05.006 · Cited by 212 · see citing works
Self-citationConnecting aging biology and inflammation in the omics era
Walker, K. A., Basisty, N., Wilson, D. M., & Ferrucci, L. (2022) · Journal of Clinical Investigation · doi:10.1172/jci158448 · Cited by 189 · see citing works
“A p21/ Rb pathway also produces a p21-activated secretory phenotype (PASP) that directs a CXCL14-mediated mechanism of senescent cell immunosurveillance (34).”
BackgroundP16INK4A—More Than a Senescence Marker
Safwan‐Zaiter, H., Wagner, N., & Wagner, K. (2022) · Life · doi:10.3390/life12091332 · Cited by 185 · see citing works
“Additionally, the SASPs of p16 and p21 cells are functionally different [87].”
BackgroundHan, Z., Wang, K., Ding, S., & Zhang, M. (2024) · Bone Research · doi:10.1038/s41413-024-00375-z · Cited by 189 · see citing works
The role of p21 in cellular senescence and aging-related diseases
Yan, J., Chen, S., Yi, Z., Zhao, R., Zhu, J., Shuwen, D., & Wu, J. (2024) · Molecules and Cells · doi:10.1016/j.mocell.2024.100113 · Cited by 181 · see citing works
“It aids in clearing stressed cells, and when the stress surpasses the cell ’ s repair capacity, p21 releases chemokines such as CXCL14 to recruit macrophages and maintain multicellular environment homeostasis (Sturmlechner et al., 2021).”
The Senescence Markers p16INK4A, p14ARF/p19ARF, and p21 in Organ Development and Homeostasis
Wagner, K., & Wagner, N. (2022) · Cells · doi:10.3390/cells11121966 · Cited by 156 · see citing works
Single-cell senescence identification reveals senescence heterogeneity, trajectory, and modulators
Tao, W., Yu, Z., & Han, J.-D. J. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.03.009 · Cited by 147 · see citing works
Zhu, H., Chen, J., Liu, K., Gao, L., Wu, H., Ma, L., Zhou, J., Liu, Z., & Han, J. J. (2023) · Science Advances · doi:10.1126/sciadv.abq7599 · Cited by 147 · see citing works
SGLT2 inhibition eliminates senescent cells and alleviates pathological aging
Katsuumi, G., Shimizu, I., Suda, M., Yoshida, Y., Furihata, T., Joki, Y., Hsiao, C.-L., Liang, J., Fujiki, S., Abe, M., et al. (2024) · Nature Aging · doi:10.1038/s43587-024-00642-y · Cited by 145 · 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
A link between mitotic defects and mitotic catastrophe: detection and cell fate
Sazonova, E. V., Петричук, С. В., Kopeina, G. S., & Zhivotovsky, B. (2021) · Biology Direct · doi:10.1186/s13062-021-00313-7 · Cited by 134 · see citing works
Murakami, T., Inagaki, N., & Kondoh, H. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.869414 · Cited by 134 · see citing works
Vitamin C epigenetically controls osteogenesis and bone mineralization
Thaler, R., Khani, F., Sturmlechner, I., Dehghani, S. S., Denbeigh, J. M., Zhou, X., Pichurin, O., Dudakovic, A., Jerez, S., Zhong, J., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32915-8 · Cited by 122 · see citing works
Self-citationType 2 cytokine signaling in macrophages protects from cellular senescence and organismal aging
Zhou, Z., Yao, J., Wu, D., Huang, X., Wang, Y., Li, X., Lu, Q., & Qiu, Y. (2024) · Immunity · doi:10.1016/j.immuni.2024.01.001 · Cited by 120 · see citing works
Xu, P., Wang, M., Song, W.-M., Wang, Q., Yuan, G.-C., Sudmant, P. H., Zare, H., Tu, Z., Orr, M. E., & Zhang, B. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00507-7 · Cited by 114 · see citing works
“1% (103) of these SASP factors were upregulated in the senescent human fetal lung (IMR-90) cells induced by γ-irradiation (Table S7) [66].”
BackgroundReshaping 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
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
Role of cellular senescence in inflammation and regeneration
Saito, Y., Yamamoto, S., & Chikenji, T. (2024) · Inflammation and Regeneration · doi:10.1186/s41232-024-00342-5 · Cited by 117 · see citing works
“…not only maintains the cell cycle arrest of senescent cells but also mobilizes macrophages by secreting CXCL14 as a p21-activated secretory phenotype, polarizing them into M1-type macrophages, and inducing a system by which senescent cells are eliminated by cytotoxic T cell recruitment [111].”
BackgroundChromatin basis of the senescence-associated secretory phenotype
Hao, X., Wang, C., & Zhang, R. (2022) · Trends in Cell Biology · doi:10.1016/j.tcb.2021.12.003 · Cited by 94 · see citing works
IRF3 activates RB to authorize cGAS-STING–induced senescence and mitigate liver fibrosis
Wu, Q., Leng, X., Zhang, Q., Zhu, Y., Zhou, R., Liu, Y., Chen, M., Zhang, D., Liu, S., Chen, S., et al. (2024) · Science Advances · doi:10.1126/sciadv.adj2102 · Cited by 98 · see citing works
Sun, Y., Mu, S., Xing, Z., Guo, J., Wu, Z., Yu, F., Bai, M., Han, X., Cheng, C., & Ye, L. (2022) · Advanced Materials · doi:10.1002/adma.202206208 · Cited by 92 · see citing works
The role of p53 in anti-tumor immunity and response to immunotherapy
Carlsen, L., Zhang, S., Tian, X., Cruz, A. D. L., George, A., Arnoff, T. E., & El‐Deiry, W. S. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2023.1148389 · Cited by 92 · see citing works
“Notably, p21 overexpression recruited macrophages, T-cells, and B cells, but did not have any effect on NK cell recruitment (Sturmlechner et al., 2021).”
Backgroundp21 induces a senescence program and skeletal muscle dysfunction
Englund, D. A., Jolliffe, A., Aversa, Z., Zhang, X., Sturmlechner, I., Sakamoto, A. E., Zeidler, J. D., Warner, G. M., McNinch, C., White, T. A., et al. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101652 · Cited by 90 · see citing works
“The generation of a robust SASP is consistent with the recent observation that p21, when elevated, induces an immediate secretory phenotype, referred to as the p21-associated secretory phenotype or PASP, which becomes an integral part of the SASP once damaged or stressed cells enter a senescent state [16].”
BackgroundSelf-citationPotential Regulators of the Senescence-Associated Secretory Phenotype During Senescence and Aging
Han, X., Lei, Q., Xie, J., Liu, H., Li, J., Zhang, X., Zhang, T., & Gou, X. (2022) · The Journals of Gerontology Series A · doi:10.1093/gerona/glac097 · Cited by 96 · see citing works
Local senolysis in aged mice only partially replicates the benefits of systemic senolysis
Farr, J. N., Saul, D., Doolittle, M. L., Kaur, J., Rowsey, J. L., Vos, S. J., Froemming, M. N., Lagnado, A. B., Zhu, Y., Weivoda, M., et al. (2023) · Journal of Clinical Investigation · doi:10.1172/jci162519 · Cited by 81 · see citing works
“With aging, SnCs have increased expression of p16Ink4a in several mammalian tissues (20), whereas p21Cip1 seems to be induced by cells under acute duress leading to senescence in other circumstances (21), including tissue repair (22, 23).”
BackgroundHepatocellular senescence induces multi-organ senescence and dysfunction via TGFβ
Kiourtis, C., Terradas-Terradas, M., Gee, L., May, S., Γεωργακοπούλου, Α., Collins, A., O'Sullivan, E. D., Baird, D., Hassan, M., Shaw, R., et al. (2024) · Nature Cell Biology · doi:10.1038/s41556-024-01543-3 · Cited by 85 · see citing works
Ding, F., Lu, L., Wu, C., Pan, X., Liu, B., Zhang, Y., Wang, Y., Wu, W., Yan, B., Zhang, Y., et al. (2022) · Theranostics · doi:10.7150/thno.77630 · Cited by 81 · see citing works
“showed that one-third of the aging-related gene expression is p21 dependent [58].”
BackgroundCellular senescence and the host immune system in aging and age-related disorders
Giannoula, Y., Kroemer, G., & Pietrocola, F. (2023) · Biomedical Journal · doi:10.1016/j.bj.2023.02.001 · Cited by 81 · see citing works
“In linewith this tenet, preneoplastic p21þ cells detected in the liver following KRAS activation are placed under immunosurveillance and progressively cleared by host immune cells shortly after induction [22].”
BackgroundInfluentialThe 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
“Senes-cent hepatocytes/stellate cells have been shown to drive the polarization of macrophages toward an M1 phenotype, effective in containing liver tumor growth, through a SASP regulated by persistent p21 (Cdkn1a) expression [115].”
BackgroundCellular senescence in brain aging and cognitive decline
Shafqat, A., Khan, S., Omer, M. H., Niaz, M., Albalkhi, I., AlKattan, K. M., Yaqinuddin, A., Tchkonia, T., Kirkland, J. L., & Hashmi, S. K. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1281581 · Cited by 75 · see citing works
Endothelial Senescence: A New Age in Pulmonary Hypertension
Culley, M. K., & Chan, S. Y. (2022) · Circulation Research · doi:10.1161/circresaha.121.319815 · Cited by 71 · see citing works
TGF-β in the microenvironment induces a physiologically occurring immune-suppressive senescent state
Matsuda, S., Revandkar, A., Dubash, T. D., Ravi, A., Wittner, B. S., Lin, M., Morris, R. T., Burr, R., Guo, H., Seeger, K., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112129 · Cited by 71 · see citing works
“…INK4A; wild-type p53) and TE4 (mutant p53), respectively (Figure S1C). p21 protein, contributing to cellular senescence by inhibiting the activity of cyclin-dependent kinases (CDKs) such as CDK2 and CDK4, 37,38 was suppressed by 10-fold in hypoxic cells compared with normoxic cells (Figure 1B).”
Cherry, C., Andorko, J. I., Krishnan, K., Mejías, J. C., Nguyen, H. H., Stivers, K. B., Gray-Gaillard, E. F., Ruta, A., Han, J., Hamada, N., et al. (2023) · GeroScience · doi:10.1007/s11357-023-00785-7 · Cited by 66 · see citing works
“Cells were harvested and subjected to downstream applications as described previously [33].”
BackgroundMethodInfluentialSelf-citationLyons, C. E., Razzoli, M., & Bartolomucci, A. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105359 · Cited by 74 · see citing works
p53 in senescence – it's a marathon, not a sprint
Sheekey, E., & Narita, M. (2021) · FEBS Journal · doi:10.1111/febs.16325 · Cited by 63 · see citing works
Stress-induced β cell early senescence confers protection against type 1 diabetes
Lee, H., Sahin, G. S., Chen, C.-W., Sonthalia, S., Cañas, S. M., Oktay, H. Z., Duckworth, A. T., Brawerman, G. M., Thompson, P. J., Hatzoglou, M., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.10.014 · Cited by 65 · see citing works
Ruggiero, A. D., Vemuri, R., Blawas, M., Long, M., DeStephanis, D., Williams, A. G., Chen, H., Justice, J. N., Macauley, S. L., Day, S. M., et al. (2023) · GeroScience · doi:10.1007/s11357-023-00830-5 · Cited by 63 · see citing works
“Similarly, p21 expression acts as a mechanism of immunosurveillance and results in polarization of M1 macrophages, which recruit cytotoxic T cells that facilitate targeted cell removal to maintain tissue homeostasis [52].”
BackgroundCellular Senescence in Aging Lungs and Diseases
Aghali, A., Ngassie, M. L. K., Pabelick, C. M., & Prakash, Y. S. (2022) · Cells · doi:10.3390/cells11111781 · Cited by 64 · see citing works
“Although upregulation of p16ink4a is meditated by the downstream signaling of p53-p21CIP1 [29,31,32,43,52], it is believed that the transcriptional factor p21CIP1 upregulates earlier than p16 ink4a [47], giving a chance for cultured cells to go for another division cycle before making it to a complete cell cycle arres…”
BackgroundRing, N., Valdivieso, K., Grillari, J., Redl, H. R., & Ogrodnik, M. B. (2022) · Developmental Cell · doi:10.1016/j.devcel.2022.04.005 · Cited by 57 · see citing works
Liu, X., Lu, Y., Huang, J., Xing, Y., Dai, H., Zhu, L., Li, S., Feng, J., Zhou, B., Li, J., et al. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.10.015 · Cited by 59 · see citing works
Liu, Y., Dou, Y., Sun, X., & Yang, Q. (2024) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2024.02.003 · Cited by 57 · see citing works
“It has also been shown to produce SASP through retinoblastoma protein (Rb)-dependent transcription and activate immune surveillance of senescent cells [52].”
BackgroundDu, K., Umbaugh, D. S., Wang, L., Jun, J. H., Dutta, R. K., Oh, S., Ren, N., Zhang, Q., Ko, D. C., Ferreira, A., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-57616-w · Cited by 60 · see citing works
“Previous investigations have described P21 as an early event to halt cell cycle progression, particularly in the liver 17,62 .”
Mapping epidermal and dermal cellular senescence in human skin aging
Yu, G., Gânier, C., Allison, D. B., Tchkonia, T., Khosla, S., Kirkland, J. L., Lynch, M. D., & Wyles, S. P. (2024) · Aging Cell · doi:10.1111/acel.14358 · Cited by 54 · see citing works
Pancreatic β-cell senescence in diabetes: mechanisms, markers and therapies
Cha, J., Aguayo‐Mazzucato, C., & Thompson, P. J. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1212716 · Cited by 51 · see citing works
“Frontiers in Endocrinology 08 not p16 Ink4a -driven SASP is sufficient to trigger immune surveillance and removal of senescent cells in vivo (92).”
BackgroundSubcellular structure, heterogeneity, and plasticity of senescent cells
Bitencourt, T. C., Vargas, J. E., Silva, A. O., Fraga, L. R., & Filippi‐Chiela, E. C. (2024) · Aging Cell · doi:10.1111/acel.14154 · Cited by 46 · see citing works
“Potential players mediating the transcriptional heterogeneity of SnCs include the AP-1 transcription factor (Martínez-Zamudio et al., 2020) and the H3-specific demethylase KDM4 (Zhang et al., 2021).”
BackgroundSenescent cells limit p53 activity via multiple mechanisms to remain viable
Sturmlechner, I., Sine, C. C., Jeganathan, K. B., Zhang, C., Velasco, R. O. F., Baker, D. J., Li, H., & van Deursen, J. M. (2022) · Nature Communications · doi:10.1038/s41467-022-31239-x · Cited by 45 · see citing works
Self-citationYou, Y., Yuan, H., Min, H., Li, C. R., & Chen, J. (2023) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2023.132489 · Cited by 44 · see citing works
Han, J. J. (2023) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2023.09.007 · Cited by 45 · see citing works
IL-4 drives exhaustion of CD8+ CART cells
Stewart, C. M., Siegler, E. L., Sakemura, R. L., Cox, M. J., Huynh, T., Kimball, B. L., Mai, L., Can, İ., Roman, C. M., Yun, K., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-51978-3 · Cited by 43 · see citing works
Self-citationImmune surveillance of senescent cells in aging and disease
Majewska, J., & Krizhanovsky, V. (2025) · Nature Aging · doi:10.1038/s43587-025-00910-5 · Cited by 50 · see citing works
“…of senescent cells is tightly controlled by a p21-dependent cell-intrinsic biological timer mechanism that controls the fate of senescent cells 37 . p21 activates retinoblastoma (RB) protein-dependent transcription to affect secretory phenotypes, including cytokines, chemokines and…”
Age-Related Changes in the Fibroblastic Differon of the Dermis: Role in Skin Aging
Zorina, A. I., Zorin, V. L., Kudlay, D. A., & Kopnin, P. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23116135 · Cited by 45 · see citing works
“Otherwise, macrophages mobilize cytotoxic T lymphocytes, which promote the elimination of damaged cells [67].”
BackgroundMorris, Z. S., Demaria, S., Monjazeb, A. M., Formenti, S. C., Weichselbaum, R. R., Welsh, J. D., Enderling, H., Schoenfeld, J. D., Brody, J., McGee, H. M., et al. (2025) · The Lancet Oncology · doi:10.1016/s1470-2045(24)00656-9 · Cited by 46 · see citing works
Cellular senescence in liver diseases: From molecular drivers to therapeutic targeting
Du, K., Umbaugh, D. S., Ren, N., & Diehl, A. M. (2025) · Journal of Hepatology · doi:10.1016/j.jhep.2025.08.021 · Cited by 42 · see citing works
Senescent cells at the crossroads of aging, disease, and tissue homeostasis
Kuehnemann, C., & Wiley, C. D. (2023) · Aging Cell · doi:10.1111/acel.13988 · Cited by 41 · see citing works
“The SASP can vary with time, cell type, and inducer— adding additional complexity and contextual nuance to an already complex process (Basisty et al., 2020; Coppe et al., 2008, 2010; Hernandez-Segura et al., 2017; Sturmlechner et al., 2021; Wiley et al., 2016).”
BackgroundLossaint, G., Horvat, A., Gire, V., Bačević, K., Mrouj, K., Charrier‐Savournin, F., Georget, V., Fisher, D., & Dulić, V. (2022) · Journal of Cell Science · doi:10.1242/jcs.259114 · Cited by 40 · see citing works
Oridonin inhibits SASP by blocking p38 and NF-κB pathways in senescent cells
Yasuda, S., Horinaka, M., Iizumi, Y., Goi, W., Sukeno, M., & Sakai, T. (2021) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2021.12.098 · Cited by 39 · see citing works
Miller, K. N., Li, B., Pierce-Hoffman, H. R., Patel, S., Lei, X., Rajesh, A., Teneche, M. G., Havas, A. P., Gandhi, A., Macip, C. C., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-57229-3 · Cited by 41 · see citing works
Age-Related Midbrain Inflammation and Senescence in Parkinson’s Disease
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“It has been shown that p21, a potent cyclindependent kinase inhibitor that regulates cell proliferation, plays an important role in SASP expression which can induce immunosurveillance of senescent cells to recruit macrophages as a first line of defense (Sturmlechner et al., 2021).”
BackgroundDistinct senotypes in p16- and p21-positive cells across human and mouse aging tissues
Saul, D., Jurk, D., Doolittle, M. L., Kosinsky, R. L., Han, Y., Zhang, X., Franco, A. C., Kim, S. Y., Wyles, S. P., Prakash, Y. S., et al. (2025) · The EMBO Journal · doi:10.1038/s44318-025-00601-2 · Cited by 45 · see citing works
“This is in line with previous studies in which overexpression of p21 or p16 in mouse embryonic fi broblasts led to distinct secretome pro fi les (Sturmlechner et al, 2021), showing only partial overlap (Fig.”
Zhang, X., Ng, Y. E., Chini, L., Heeren, A. A., White, T. A., Li, H., Huang, H., Doolittle, M. L., Khosla, S., & LeBrasseur, N. K. (2023) · Aging Cell · doi:10.1111/acel.14069 · Cited by 37 · see citing works
“In the context of health, immune cells facilitate the removal of senescent cells, while in disease they can instead amplify the proinflammatory SASP (Behmoaras & Gil, 2021; Sturmlechner et al., 2021).”
BackgroundSelf-citationMonroe, T. B., Hertzel, A. V., Dickey, D. M., Hagen, T., Santibanez, S. V., Berdaweel, I. A., Halley, C. L., Puchalska, P., Anderson, E. J., Camell, C. D., et al. (2024) · Aging Cell · doi:10.1111/acel.14367 · Cited by 40 · see citing works
“…across different human se - nescence models, we cross-referenced our dataset with two other published datasets on ionizing radiation-induced senescence and replicative senescence (Casella et al., 2019; Sturmlechner et al., 2021 ) focusing on those with at least a 2-fold change in expres - sion.”
IL-23R is a senescence-linked circulating and tissue biomarker of aging
Carver, C. M., Rodriguez, S. L., Atkinson, E. J., Dosch, A. J., Asmussen, N. C., Gomez, P. T., Leitschuh, E. A., Espíndola‐Netto, J. M., Jeganathan, K. B., Whaley, M. G., et al. (2024) · Nature Aging · doi:10.1038/s43587-024-00752-7 · Cited by 37 · see citing works
Self-citationRecent insights into the crosstalk between senescent cells and CD8 T lymphocytes
Marín, I., Serrano, M., & Pietrocola, F. (2023) · npj Aging · doi:10.1038/s41514-023-00105-5 · Cited by 39 · see citing works
Cellular senescence and neurodegeneration
Holloway, K., Neherin, K., Dam, K. U., & Zhang, H. (2023) · Human Genetics · doi:10.1007/s00439-023-02565-x · Cited by 40 · see citing works
Context‐dependent roles of cellular senescence in normal, aged, and disease states
Moiseeva, V., Cisneros, A., Cobos, A. C., Tarrega, A. B., Oñate, C. S., Perdiguero, E., Serrano, A. L., & Muñoz‐Cánoves, P. (2023) · The FEBS Journal · doi:10.1111/febs.16573 · Cited by 34 · 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
Marongiu, F., & DeGregori, J. V. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13275 · Cited by 35 · see citing works
Brown, J. S. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104809 · Cited by 33 · see citing works
Erlangga, Z., Ghashang, S. K., Hamdan, I., Melk, A., Gutenbrunner, C. M., & Nugraha, B. (2023) · Human Nutrition & Metabolism · doi:10.1016/j.hnm.2023.200189 · Cited by 36 · see citing works
Chen, W., Wang, Y., Zheng, J., Chen, Y., Zhang, C., Yang, W. C., Wu, L., Yang, Z., Wang, Y., & Shi, C. (2023) · Burns & Trauma · doi:10.1093/burnst/tkad001 · Cited by 32 · see citing works
“The latest research has reported that in addition to the classical role of cell cycle arrest, p21 may act as a monitoring mechanism for maintaining homeostasis after stress or injury [29], which may be the reason why the level of p16 was increased earlier than that of p21.”
BackgroundSelf-citationT cell fate decisions during memory cell generation with aging
Sturmlechner, I., Jain, A. K., Mu, Y., Weyand, C. M., & Goronzy, J. J. (2023) · Seminars in Immunology · doi:10.1016/j.smim.2023.101800 · Cited by 31 · see citing works
Self-citationRentschler, M., Braumüller, H., Briquez, P. S., & Wieder, T. (2022) · Cancers · doi:10.3390/cancers14061364 · Cited by 31 · see citing works
Song, J., Zhu, J. W., Jiang, Y., Guo, Y., Liu, S., Qiao, Y., Du, Y., & Li, J. (2025) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2025.189277 · Cited by 30 · see citing works
Extra centrosomes induce PIDD1‐mediated inflammation and immunosurveillance
García-Carpio, I., Braun, V. Z., Weiler, E. S., Leone, M., Niñerola, S., Barco, Á., Fava, L. L., & Villunger, A. (2023) · The EMBO Journal · doi:10.15252/embj.2023113510 · Cited by 28 · see citing works
“…transcripts upregulated after cytokinesis failure (Fig 1), we found Ccl2 , Ccl7 , and Cxcl14 , well-known chemokines that act as positive attractors of NK cells and other innate immune cell types, such as macrophages (Morrison et al , 2003; Hara & Tanegashima, 2012; Sturmlechner et al , 2021).”
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
“CXCL14 from SASP enables a dominant macrophage-based immunosurveillance of KRASG12V-induced senescent hepatocytes, acting as a barrier against HCC outgrowth [85].”
Backgroundp21 regulates expression of ECM components and promotes pulmonary fibrosis via CDK4 and Rb
Papismadov, N., Levi, N., Roitman, L., Agrawal, A., Ovadya, Y., Cherqui, U., Yosef, R., Akiva, H., Gal, H., & Krizhanovsky, V. (2024) · The EMBO Journal · doi:10.1038/s44318-024-00246-7 · Cited by 30 · see citing works
“Indeed, hypo-phosphorylated Rb can bind to Smad-3 and upregulate its transcriptional activity (Sturmlechner et al, 2021).”
InfluentialShrestha, N., Chaturvedi, P., Zhu, X., Dee, M. J., George, V., Janney, C., Egan, J. O., Liu, B., Foster, M., Marsala, L. I., et al. (2023) · Aging Cell · doi:10.1111/acel.13806 · Cited by 27 · see citing works
“We hypothesize that this global effect in the liver is the result of removal of p21+ SNCs mediated by HCW9218- activated immune cells. p21, in addition to its function in maintaining the cell cycle- arrest in SNCs, is known to have a prominent role in establishing SASP (Sturmlechner et al., 2021).”
BackgroundDistinct secretomes in p16- and p21- positive senescent cells across tissues
Saul, D., Jurk, D., Doolittle, M. L., Kosinsky, R. L., Monroe, D. G., LeBrasseur, N. K., Robbins, P. D., Niedernhofer, L. J., Khosla, S., & Passos, J. F. (2023) · doi:10.1101/2023.12.05.569858 · Cited by 28 · see citing works
Wang, J., Zhou, X., Yu, P., Yao, J., Guo, P., Xu, Q., Zhao, Y., Wang, G., Li, Q., Zhu, X., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00886-2 · Cited by 28 · see citing works
Senescence landscape in the liver following sepsis and senolytics as potential therapeutics
Lavarti, R., Cai, L., Alvarez‐Diaz, T., Medina‐Rodriguez, T., Bombin, S., & Raju, R. P. (2024) · Aging Cell · doi:10.1111/acel.14354 · Cited by 27 · see citing works
“In a recent study, it was shown that p21, through Rb hypophosphorylation, induces CXCL14, a macrophage attractant chemokine, thereby recruiting and differentiating macrophages to the senescent tissue foci (Sturmlechner et al., 2021).”
Immunosenescence and macrophages: From basics to therapeutics
Zhu, H., Shen, F., Liao, T., Qian, H., & Liu, Y. (2023) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2023.106479 · Cited by 28 · see citing works
Umbaugh, D. S., Nguyen, N. T., Smith, S. H., Ramachandran, A., & Jaeschke, H. (2024) · Toxicology · doi:10.1016/j.tox.2024.153804 · Cited by 26 · see citing works
Aging reshapes the adaptive immune system from healer to saboteur
Delgado-Pulido, S., Yousefzadeh, M. J., & Mittelbrunn, M. (2025) · Nature Aging · doi:10.1038/s43587-025-00906-1 · Cited by 29 · see citing works
“It is well established that innate immune cells, such as natural killer (NK) cells and macrophages, are responsible for eliminating senescent cells, whereas the role of adaptive immunity in this process is only beginning to be understood 24 .”
Palacios, Y., Ramón‐Luing, L. A., Ruíz, A., García-Martínez, A., Sánchez-Monciváis, A., Barreto-Rodríguez, O., Falfán‐Valencia, R., Pérez-Rubio, G., Quero, K. M., Buendía-Roldán, I., et al. (2023) · Microbes and Infection · doi:10.1016/j.micinf.2023.105179 · 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
The origins of cancer cell dormancy
Morales-Valencia, J., & David, G. (2022) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2022.101914 · Cited by 25 · see citing works
Genetic origins, regulators, and biomarkers of cellular senescence
Torres, G., Salladay-Perez, I. A., Dhingra, A., & Covarrubias, A. J. (2024) · Trends in Genetics · doi:10.1016/j.tig.2024.08.007 · Cited by 24 · see citing works
Braumüller, H., Mauerer, B., Berlin, C., Plundrich, D., Marbach, P., Cauchy, P., Laessle, C., Biesel, E. A., Holzner, P. A., & Kesselring, R. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.908449 · Cited by 24 · see citing works
“The composition of SASP greatly varies dependent on the cell type and on the inducer of the senescence (41, 42).”
BackgroundZhang, Z., Wu, Q., Fang, M., Liu, Y., Jiang, J., Feng, Q., Hu, R., & Xu, J. (2022) · International Journal of Biological Sciences · doi:10.7150/ijbs.72014 · Cited by 24 · see citing works
de Queiroz, R. M., Moon, S.-H., & Prives, C. L. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102289 · Cited by 24 · see citing works
“In line with this, since p21 was recently reported to induce immune surveillance (39), OSMI-1 may have additional benefits for cancer treatment.”
BackgroundTranscriptional Heterogeneity of Cellular Senescence in Cancer
Junaid, M., Lee, A., Kim, J., Park, T. J., & Lim, S. B. (2022) · Molecules and Cells · doi:10.14348/molcells.2022.0036 · Cited by 24 · see citing works
“Although SASPs are secreted from cells after cell cycle arrest (Herranz and Gil, 2018), cell cycle arrest and PASP are concurrently established, at least in hepatocytes (Sturmlechner et al., 2021).”
BackgroundInfluentialA review focusing on the benefits of plant-derived polysaccharides for osteoarthritis
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Phytochemicals as Epigenetic Modulators in Chronic Diseases: Molecular Mechanisms
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Endothelial senescent-cell-specific clearance alleviates metabolic dysfunction in obese mice
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Senescent cells as thermostats of antitumor immunity
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Self-citationResearch progress on interferon and cellular senescence
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“58,59 P53 is a transcription factor that primarily mediates genomic damage-induced senescence.”
- Authors
- Sturmlechner, I., Zhang, C., Sine, C. C., van Deursen, E.-J., Jeganathan, K. B., Hamada, N., Grasic, J., Friedman, D., Stutchman, J. T., Can, I., Hamada, M., Lim, D. Y., Lee, J.-H., Ordog, T., Laberge, R.-M., Shapiro, V., Baker, D. J., Li, H., & van Deursen, J. M.
- Affiliations
- Mayo Clinic (US)
- Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA.
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
- Epigenomics Program, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
- Unity Biotechnology, South San Francisco, CA 94080, USA.
- Corresponding author
- Li, Hu
- ORCID
- Venue
- Science
- Published
- 2021-10-29
- Volume
- 374
- Issue
- 6567
- Pages
- eabb3420-eabb3420
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC8985214
- OpenAlex
- W3208518221
- Cited by
- 295
- References
- 74
- Citations by year
- 2026: 60 · 2025: 65 · 2024: 59 · 2023: 53 · 2022: 54 · 2021: 4
- FWCI
- 15.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- Mayo Clinic (P30 DK084567)
- W. M. Keck Foundation
- Glenn Foundation for Medical Research
- Fondation pour la Recherche Médicale
- National Institutes of Health (DK084567)
- Center for Cell Signaling in Gastroenterology, Mayo Clinic (P30 DK084567, DK084567)
- National Institute on Aging (RF1AG056318, R01AG057493, R01AG050618)
- National Cancer Institute (R01CA196631, R01CA208517, R01CA096985, P30CA015083)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK058185, P30DK084567)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- p21, immune surveillance, secretome, retinoblastoma protein, CXCL14, macrophage polarization, M1 macrophages, cytotoxic T lymphocytes, cell cycle arrest, preneoplastic cells, tumor immunology, cell fate
- MeSH terms
- Animals, Cell Line, Humans, Immunologic Surveillance, Macrophages, Mice, Transgenic, Genes, ras, Stress, Physiological, T-Lymphocytes, Cytotoxic, Transcription, Genetic, Retinoblastoma Protein, Proto-Oncogene Proteins p21(ras), Cellular Senescence, Chemokines, CXC, Cyclin-Dependent Kinase Inhibitor p16, Hepatocytes, Cyclin-Dependent Kinase Inhibitor p21, Mice, Cell Cycle Checkpoints
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