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Blocking PD-L1–PD-1 improves senescence surveillance and ageing phenotypes

Wang, Teh-Wei, Johmura, Yoshikazu, Suzuki, Narumi, Omori, Satotaka, Migita, Toshiro, Yamaguchi, Kiyoshi, Hatakeyama, Seira, Yamazaki, Satoshi, Shimizu, Eigo, Imoto, Seiya, Furukawa, Yoichi, Yoshimura, Akihiko, Nakanishi, Makoto·2022·Nature
DOI 10.1038/s41586-022-05388-4
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Abstract

The accumulation of senescent cells is a major cause of age-related inflammation and predisposes to a variety of age-related diseases 1 . However, little is known about the molecular basis underlying this accumulation and its potential as a target to ameliorate the ageing process. Here we show that senescent cells heterogeneously express the immune checkpoint protein programmed death-ligand 1 (PD-L1) and that PD-L1 + senescent cells accumulate with age in vivo. PD-L1 - cells are sensitive to T cell surveillance, whereas PD-L1 + cells are resistant, even in the presence of senescence-associated secretory phenotypes (SASP). Single-cell analysis of p16 + cells in vivo revealed that PD-L1 expression correlated with higher levels of SASP. Consistent with this, administration of programmed cell death protein 1 (PD-1) antibody to naturally ageing mice or a mouse model with normal livers or induced nonalcoholic steatohepatitis reduces the total number of p16 + cells in vivo as well as the PD-L1 + population in an activated CD8 + T cell-dependent manner, ameliorating various ageing-related phenotypes. These results suggest that the heterogeneous expression of PD-L1 has an important role in the accumulation of senescent cells and inflammation associated with ageing, and the elimination of PD-L1 + senescent cells by immune checkpoint blockade may be a promising strategy for anti-ageing therapy.

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  1. Johmura, Y. et al. Necessary and sufficient role for a mitosis skip in senescence induction. Mol. Cell 55, 73–84 (2014). · DOI · Paper page
  2. Pieren, D. K. J., Smits, N. A. M., van de Garde, M. D. B. & Guichelaar, T. Response kinetics reveal novel features of ageing in murine T cells. Sci. Rep. 9, 5587 (2019). · DOI
  3. Lages, C. S., Lewkowich, I., Sproles, A., Wills-Karp, M. & Chougnet, C. Partial restoration of T-cell function in aged mice by in vitro blockade of the PD-1/PD-L1 pathway. Aging Cell 9, 785–798 (2010). · DOI
  4. Channappanavar, R., Twardy, B. S., Krishna, P. & Suvas, S. Advancing age leads to predominance of inhibitory receptor expressing CD4 T cells. Mech. Ageing Dev. 130, 709–712 (2009). · DOI
  5. Decman, V. et al. Defective CD8 T cell responses in aged mice are due to quantitative and qualitative changes in virus-specific precursors. J. Immunol. 188, 1933–1941 (2012). · DOI
  6. Helmbold, H., Kömm, N., Deppert, W. & Bohn, W. Rb2/p130 is the dominating pocket protein in the p53–p21 DNA damage response pathway leading to senescence. Oncogene 28, 3456–3467 (2009). · DOI
  7. Fan, J. & Bertino, J. R. Functional roles of E2F in cell cycle regulation. Oncogene 14, 1191–1200 (1997). · DOI
  8. Dyson, N., Guida, P., Münger, K. & Harlow, E. Homologous sequences in adenovirus E1A and human papillomavirus E7 proteins mediate interaction with the same set of cellular proteins. J. Virol. 66, 6893–6902 (1992). · DOI
  9. Verfaillie, A., Imrichova, H., Janky, R. & Aerts, S. iRegulon and i-cisTarget: reconstructing regulatory networks using motif and track enrichment. Curr. Protoc. Bioinformatics 52, 2 (2015). · DOI
  10. Lim, S. O. et al. Deubiquitination and stabilization of PD-L1 by CSN5. Cancer Cell 30, 925–939 (2016). · DOI · Paper page
  11. Rechsteiner, M. & Hill, C. P. Mobilizing the proteolytic machine: cell biological roles of proteasome activators and inhibitors. Trends Cell Biol. 15, 27–33 (2005). · DOI
  12. Radhakrishnan, S. K. et al. Transcription factor Nrf1 mediates the proteasome recovery pathway after proteasome inhibition in mammalian cells. Mol. Cell 38, 17–28 (2010). · DOI · Paper page
  13. Zhang, Y. & Hayes, J. D. The membrane-topogenic vectorial behaviour of Nrf1 controls its post-translational modification and transactivation activity. Sci. Rep. 3, 2006 (2013). · DOI
  14. Kalbasi, A. et al. Uncoupling interferon signaling and antigen presentation to overcome immunotherapy resistance due to JAK1 loss in melanoma. Sci. Transl. Med. 12, eabb0152 (2020). · DOI
  15. Grosse, L. et al. Defined p16High senescent cell types are indispensable for mouse healthspan. Cell Metab. 32, 87–99.e6 (2020). · DOI · Paper page
  16. Maeso-Díaz, R. et al. Effects of aging on liver microcirculatory function and sinusoidal phenotype. Aging Cell 17, e12829 (2018). · DOI
  17. Vaddepally, R. K., Kharel, P., Pandey, R., Garje, R. & Chandra, A. B. Review of indications of FDA-approved immune checkpoint inhibitors per NCCN guidelines with the level of evidence. Cancers 12, 738 (2020). · DOI
  18. Liu, J. Y. et al. Cells exhibiting strong p16INK4a promoter activation in vivo display features of senescence. Proc. Natl Acad. Sci. USA 116, 2603–2611 (2019). · DOI · Paper page
  19. Schulte, H., Mühlfeld, C. & Brandenberger, C. Age-related structural and functional changes in the mouse lung. Front. Physiol. 10, 1466 (2019). · DOI
  20. Gregg, S. Q. et al. A mouse model of accelerated liver aging caused by a defect in DNA repair. Hepatology 55, 609–621 (2012). · DOI
  21. Sheth, K. A. et al. Muscle strength and size are associated with motor unit connectivity in aged mice. Neurobiol. Aging 67, 128–136 (2018). · DOI
  22. Tung, V. W. K., Burton, T. J., Quail, S. L., Mathews, M. A. & Camp, A. J. Motor performance is impaired following vestibular stimulation in ageing mice. Front. Aging Neurosci. 8, 12 (2016). · DOI
  23. Matsumoto, M. et al. An improved mouse model that rapidly develops fibrosis in non-alcoholic steatohepatitis. Int. J. Exp. Pathol. 94, 93–103 (2013). · DOI · Paper page
  24. 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
  25. Kazankov, K. et al. The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Nat. Rev. Gastroenterol. Hepatol. 16, 145–159 (2019). · DOI · Paper page
  26. McDonnell, W. J. et al. High CD8 T-cell receptor clonality and altered CDR3 properties are associated with elevated isolevuglandins in adipose tissue during diet-induced obesity. Diabetes 67, 2361–2376 (2018). · DOI
  27. Koda, Y. et al. CD8+ tissue-resident memory T cells promote liver fibrosis resolution by inducing apoptosis of hepatic stellate cells. Nat. Commun. 12, 4474 (2021). · DOI · Paper page
  28. Rosenzweig, N. et al. PD-1/PD-L1 checkpoint blockade harnesses monocyte-derived macrophages to combat cognitive impairment in a tauopathy mouse model. Nat. Commun. 10, 465 (2019). · DOI
  29. Pfister, D. et al. NASH limits anti-tumour surveillance in immunotherapy-treated HCC. Nature 592, 450–456 (2021). · DOI · Paper page
  30. Kondo, T. et al. Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy. Nat. Commun. 8, 15338 (2017). · DOI
  31. Hogquist, K. A. et al. T cell receptor antagonist peptides induce positive selection. Cell 76, 17–27 (1994). · DOI
  32. Simma, O. et al. Identification of an indispensable role for tyrosine kinase 2 in CTL-mediated tumor surveillance. Cancer Res. 69, 203–211 (2009). · DOI
  33. Merry, T. L. et al. The CSF1 receptor inhibitor pexidartinib (PLX3397) reduces tissue macrophage levels without affecting glucose homeostasis in mice. Int. J. Obesity 44, 245–253 (2020). · DOI
  34. Nakanishi, M. et al. Exit from G0 and entry into the cell cycle of cells expressing p21Sdi1 antisense RNA. Proc. Natl Acad. Sci. USA 92, 4352–4356 (1995). · DOI
  35. Parrinello, S. et al. Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts. Nat. Cell Biol. 5, 741–747 (2003). · DOI · Paper page
  36. Johmura, Y. et al. SCFFbxo22-KDM4A targets methylated p53 for degradation and regulates senescence. Nat. Commun. 7, 10574 (2016). · DOI
  37. Liao, Y., Smyth, G. K. & Shi, W. The R package Rsubread is easier, faster, cheaper and better for alignment and quantification of RNA sequencing reads. Nucleic Acids Res. 47, e47 (2019). · DOI
  38. Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139–140 (2009). · DOI · Paper page
  39. Ritchie, M. E. et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015). · DOI · Paper page
  40. Yu, G., Wang, L. G., Han, Y. & He, Q. Y. ClusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16, 284–287 (2012). · DOI · Paper page
  41. Storer, J., Hubley, R., Rosen, J., Wheeler, T. J. & Smit, A. F. The Dfam community resource of transposable element families, sequence models, and genome annotations. Mob. DNA 12, 2 (2021). · DOI
  42. Lewis, M. D. et al. A reproducible method for the expansion of mouse CD8+ T lymphocytes. J. Immunol. Methods 417, 134–138 (2015). · DOI
  43. Kitamura, T., Doughty-Shenton, D., Pollard, J. W. & Carragher, N. O. Real time detection of in vitro tumor cell apoptosis induced by CD8+ T cells to study immune suppressive functions of tumor-infiltrating myeloid cells. J. Vis. Exp. https://doi.org/10.3791/58841 (2019). · DOI

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Metadata

Authors
Wang, T.-W., Johmura, Y., Suzuki, N., Omori, S., Migita, T., Yamaguchi, K., Hatakeyama, S., Yamazaki, S., Shimizu, E., Imoto, S., Furukawa, Y., Yoshimura, A., & Nakanishi, M.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2022-11-02
Volume
611
Issue
7935
Pages
358-364
ISSN
  • 0028-0836
  • 1476-4687
DOI
10.1038/s41586-022-05388-4
Cited by
469
References
21
Language
en
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