The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
A ganglioside-based immune checkpoint enables senescent cells to evade immunosurveillance during aging
Abstract
Although senescent cells can be eliminated by the immune system, they tend to accumulate with age in various tissues. Here we show that senescent cells can evade immune clearance by natural killer (NK) cells by upregulating the expression of the disialylated ganglioside GD3 at their surface. The increased level of GD3 expression on senescent cells that naturally occurs upon aging in liver, lung, kidney or bones leads to a strong suppression of NK-cell-mediated immunosurveillance. In mice, we found that targeting GD3 + senescent cells with anti-GD3 immunotherapy attenuated the development of experimentally induced or age-related lung and liver fibrosis and age-related bone remodeling. These results demonstrate that GD3 upregulation confers immune privilege to senescent cells. We propose that GD3 acts as a senescence immune checkpoint (SIC) that allows senescent cells to escape immunosurveillance and to trigger immune anergy during aging.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In murine models of fibrosis, anti-GD3 immunotherapy disrupted this immune tolerance, resulting in a marked reduction of SnC burden and improved tissue function9.”
From Emerging strategies in senotherapeutics: from broad-spectrum senolysis to precision reprogramming (2026) · cites this paper as [9]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“circumvents immune-mediated clearance by upregulating pro-survival and immune checkpoint pathways”
From Emerging strategies in senotherapeutics: from broad-spectrum senolysis to precision reprogramming (2026) · cites this paper as [9]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“GD3 is upregulated on the surface of SnCs in aging tissues and engages inhibitory Siglec receptors (e.g., Siglec-7) on natural killer (NK) cells, thereby suppressing their cytotoxic function.”
From Emerging strategies in senotherapeutics: from broad-spectrum senolysis to precision reprogramming (2026) · cites this paper as [9]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Aging, Cellular Senescence, and Cancer
Campisi, J. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183653 · Cited by 2,954 · cited 2×
“Mechanisti-cally, the accumulation of senescent cells (SnCs) in tissues emerges as a key driver of aging and age-associated diseases 1 .”
Geroscience: Linking Aging to Chronic Disease
Kennedy, B. K., Berger, S. L., Brunet, A., Campisi, J., Cuervo, A. M., Epel, E. S., Franceschi, C., Lithgow, G. J., Morimoto, R. I., Pessin, J. E., et al. (2014) · Cell · doi:10.1016/j.cell.2014.10.039 · Cited by 2,764
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
BRAFE600-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
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
Senescence 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
Senolytic CAR T cells reverse senescence-associated pathologies
Amor, C., Feucht, J., Leibold, J., Ho, Y.-J., Zhu, C., Alonso-Curbelo, D., Mansilla-Soto, J., Boyer, J. A., Li, X., Giavridis, T., et al. (2020) · Nature · doi:10.1038/s41586-020-2403-9 · Cited by 1,098
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
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
Senescent cells evade immune clearance via HLA-E-mediated NK and CD8+ T cell inhibition
Pereira, B. I., Devine, O. P., Vukmanovic-Stejic, M., Chambers, E. S., Subramanian, P., Patel, N., Virasami, A., Sebire, N. J., Kinsler, V., Valdovinos, A., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10335-5 · Cited by 556
Flagged first, then by citations
Research works printed but not linked: 20
- Chang, J. et al. Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nat. Med. 22, 78–83 (2016). · DOI · Paper page
- Camell, C. D. et al. Senolytics reduce coronavirus-related mortality in old mice. Science 373, eabe4832 (2021). · DOI
- Iannello, A., Thompson, T. W., Ardolino, M., Lowe, S. W. & Raulet, D. H. p53-dependent chemokine production by senescent tumor cells supports NKG2D-dependent tumor elimination by natural killer cells. J. Exp. Med. 210, 2057–2069 (2013). · DOI · Paper page
- Brighton, P. J. et al. Clearance of senescent decidual cells by uterine natural killer cells in cycling human endometrium. eLife 6, 1006 (2017). · DOI · Paper page
- Schneider, J. L. et al. The aging lung: physiology, disease, and immunity. Cell 184, 1990–2019 (2021). · DOI · Paper page
- Wang, T.-W. et al. Blocking PD-L1–PD-1 improves senescence surveillance and ageing phenotypes. Nature 611, 358–364 (2022). · DOI · Paper page
- Giannoula, Y., Kroemer, G. & Pietrocola, F. Cellular senescence and the host immune system in aging and age-related disorders. Biomed. J. 46, 100581 (2023). · DOI
- Ovadya, Y. et al. Impaired immune surveillance accelerates accumulation of senescent cells and aging. Nat. Commun. 9, 5435 (2018). · DOI · Paper page
- Ziegler, D. V. et al. Cholesterol biosynthetic pathway induces cellular senescence through ERRα. NPJ Aging 10, 5 (2024). · DOI
- Nicoll, G. et al. Ganglioside GD3 expression on target cells can modulate NK cell cytotoxicity via siglec-7-dependent and -independent mechanisms. Eur. J. Immunol. 33, 1642–1648 (2003). · DOI
- Boyer, L. et al. Aging-related systemic manifestations in COPD patients and cigarette smokers. PLoS ONE 10, e0121539 (2015). · DOI
- Liang, J. et al. Hyaluronan and TLR4 promote surfactant-protein-C-positive alveolar progenitor cell renewal and prevent severe pulmonary fibrosis in mice. Nat. Med. 22, 1285–1293 (2016). · DOI · Paper page
- Cao, Z. et al. Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis. Nat. Med. 22, 154–162 (2016). · DOI
- Liberzon, A. et al. The Molecular Signatures Database hallmark gene set collection. Cell Syst. 1, 417–425 (2015). · DOI · Paper page
- Yi, M., Nissley, D. V., McCormick, F. & Stephens, R. M. ssGSEA score-based Ras dependency indexes derived from gene expression data reveal potential Ras addiction mechanisms with possible clinical implications. Sci. Rep. 10, 10258 (2020). · DOI
- Lonsdale, J. et al. The Genotype-Tissue Expression (GTEx) project. Nat. Genet. 45, 580–585 (2013). · DOI · Paper page
- Ciucanu, J. & Kerek, F. A simple and rapid method for the permethylation of carbohydrates. Carb. Res. 131, 209–217 (1984). · DOI
- Fassy, J. et al. A real-time digital bio-imaging system to quantify cellular cytotoxicity as an alternative to the standard chromium-51 release assay. Immunology 150, 489–494 (2017). · DOI
- Fassy, J., Tsalkitzi, K., Goncalves-Maia, M. & Braud, V. M. A real-time cytotoxicity assay as an alternative to the standard chromium-51 release assay for measurement of human NK and T cell cytotoxic activity. Curr. Protoc. Immunol. https://doi.org/10.1002/cpim.28 (2017). · DOI
- Krämer, A., Green, J., Pollard, J. Jr. & Tugendreich, S. Causal analysis approaches in Ingenuity Pathway Analysis. Bioinformatics 30, 523–530 (2014). · DOI · Paper page
Cited by
Sorted by citations
Emerging strategies in senotherapeutics: from broad-spectrum senolysis to precision reprogramming
Zhang, W., Song, S., Zhang, Y., Pan, Y., Hu, D., & Wang, Y. (2026) · npj Aging · doi:10.1038/s41514-026-00355-z · Cited by 6
Metadata
- Authors
- Iltis, C., Moskalevska, I., Debiesse, A., Seguin, L., Fissoun, C., Cervera, L., Moudombi, L., Ardin, M., Ferrari, A., Eliott, C., Pisani, D., Ottaviani, A., Bourinet, M., Luci, C., Gual, P., Makulyte, G., Bernard, D., Durandy, M., Duret, L. C., Hamidouche, T., Kunz, S., Croce, O., Delannoy, C., Guérardel, Y., Allain, F., Hofman, P., Benarroch-Popivker, D., Bianchini, L., Dadone-Montaudie, B., Cosson, E., Guglielmi, J., Pourcher, T., Braud, V. M., Shkreli, M., Pers, Y.-M., Jorgensen, C., Brondello, J.-M., Féral, C. C., Michallet, M.-C., Gilson, E., & Cherfils-Vicini, J.
- Venue
- Nature Aging
- Published
- 2024-12-27
- Volume
- 5
- Issue
- 2
- Pages
- 219-236
- ISSN
- 2662-8465
- PMC
- PMC11839482
- Cited by
- 59
- References
- 12
- Language
- en
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
