Activation of the transcription factor NFAT5 in the tumor microenvironment enforces CD8
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
received:
09
09
2021
accepted:
07
08
2023
medline:
27
10
2023
pubmed:
15
9
2023
entrez:
14
9
2023
Statut:
ppublish
Résumé
Persistent exposure to antigen during chronic infection or cancer renders T cells dysfunctional. The molecular mechanisms regulating this state of exhaustion are thought to be common in infection and cancer, despite obvious differences in their microenvironments. Here we found that NFAT5, an NFAT family transcription factor that lacks an AP-1 docking site, was highly expressed in exhausted CD8
Identifiants
pubmed: 37709986
doi: 10.1038/s41590-023-01614-x
pii: 10.1038/s41590-023-01614-x
doi:
Substances chimiques
Transcription Factors
0
Programmed Cell Death 1 Receptor
0
NFAT5 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1645-1653Subventions
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : 310030_182680
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : 310030_200898
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
Références
Blank, C. U. et al. Defining ‘T cell exhaustion’. Nat. Rev. Immunol. 19, 665–674 (2019).
pubmed: 31570879
pmcid: 7286441
Utzschneider, D. T. et al. T cell factor 1-expressing memory-like CD8
pubmed: 27533016
Speiser, D. E., Ho, P. C. & Verdeil, G. Regulatory circuits of T cell function in cancer. Nat. Rev. Immunol. 16, 599–611 (2016).
pubmed: 27526640
Thommen, D. S. & Schumacher, T. N. T cell dysfunction in cancer. Cancer Cell 33, 547–562 (2018).
pubmed: 29634943
pmcid: 7116508
Cheng, H., Ma, K., Zhang, L. & Li, G. The tumor microenvironment shapes the molecular characteristics of exhausted CD8
pubmed: 33662493
Siddiqui, I. et al. Intratumoral Tcf1
pubmed: 30635237
Baitsch, L. et al. Exhaustion of tumor-specific CD8
pubmed: 21555851
pmcid: 3104769
Lopez-Rodriguez, C., Aramburu, J., Rakeman, A. S. & Rao, A. NFAT5, a constitutively nuclear NFAT protein that does not cooperate with Fos and Jun. Proc. Natl Acad. Sci. USA 96, 7214–7219 (1999).
pubmed: 10377394
pmcid: 22056
Cheung, C. Y. & Ko, B. C. NFAT5 in cellular adaptation to hypertonic stress–regulations and functional significance. J. Mol. Signal 8, 5 (2013).
pubmed: 23618372
pmcid: 3655004
Kim, N. H. et al. Reactive oxygen species regulate context-dependent inhibition of NFAT5 target genes. Exp. Mol. Med. 45, e32 (2013).
pubmed: 23867654
pmcid: 3731662
Alberdi, M. et al. Context-dependent regulation of Th17-associated genes and IFNɣ expression by the transcription factor NFAT5. Immunol. Cell Biol. 95, 56–67 (2016).
pubmed: 27479742
pmcid: 5215110
Aramburu, J. & Lopez-Rodriguez, C. Regulation of inflammatory functions of macrophages and T lymphocytes by NFAT5. Front. Immunol. 10, 535 (2019).
pubmed: 30949179
pmcid: 6435587
Carmona, S. J., Siddiqui, I., Bilous, M., Held, W. & Gfeller, D. Deciphering the transcriptomic landscape of tumor-infiltrating CD8 lymphocytes in B16 melanoma tumors with single-cell RNA-seq. Oncoimmunology 9, 1737369 (2020).
pubmed: 32313720
pmcid: 7153840
Xiong, H. et al. Coexpression of inhibitory receptors enriches for activated and functional CD8
pubmed: 31064777
Jerby-Arnon, L. et al. A cancer cell program promotes T cell exclusion and resistance to checkpoint blockade. Cell 175, 984–997 (2018).
pubmed: 30388455
pmcid: 6410377
Sade-Feldman, M. et al. Defining T cell states associated with response to checkpoint immunotherapy in melanoma. Cell 176, 404 (2019).
pubmed: 30633907
pmcid: 6647017
Azizi, E. et al. Single-cell map of diverse immune phenotypes in the breast tumor microenvironment. Cell 174, 1293–13086 (2018).
pubmed: 29961579
pmcid: 6348010
Andreatta, M. et al. Interpretation of T cell states from single-cell transcriptomics data using reference atlases. Nat. Commun. 12, 2965 (2021).
pubmed: 34017005
pmcid: 8137700
Prevost-Blondel, A. et al. Tumor-infiltrating lymphocytes exhibiting high ex vivo cytolytic activity fail to prevent murine melanoma tumor growth in vivo. J. Immunol. 161, 2187–2194 (1998).
pubmed: 9725210
Martinez-Usatorre, A. et al. Enhanced phenotype definition for precision isolation of precursor exhausted tumor-infiltrating CD8 T cells. Front .Immunol. 11, 340 (2020).
pubmed: 32174925
pmcid: 7056729
Van den Eynde, B., Mazarguil, H., Lethe, B., Laval, F. & Gairin, J. E. Localization of two cytotoxic T lymphocyte epitopes and three anchoring residues on a single nonameric peptide that binds to H-2L
pubmed: 7525302
Shanker, A. et al. CD8 T cell help for innate antitumor immunity. J. Immunol. 179, 6651–6662 (2007).
pubmed: 17982055
Giordano, M. et al. Molecular profiling of CD8 T cells in autochthonous melanoma identifies Maf as driver of exhaustion. EMBO J. 34, 2042–2058 (2015).
pubmed: 26139534
pmcid: 4551351
Giordano, M. et al. The tumor necrosis factor α-induced protein 3 (TNFAIP3, A20) imposes a brake on antitumor activity of CD8 T cells. Proc. Natl Acad. Sci. USA 111, 11115–11120 (2014).
pubmed: 25024217
pmcid: 4121810
Tong, E. H. et al. Regulation of nucleocytoplasmic trafficking of transcription factor OREBP/TonEBP/NFAT5. J. Biol. Chem. 281, 23870–23879 (2006).
pubmed: 16782704
Martinez, G. J. et al. The transcription factor NFAT promotes exhaustion of activated CD8
pubmed: 25680272
pmcid: 4346317
Chen, J. et al. NR4A transcription factors limit CAR T cell function in solid tumours. Nature 567, 530–534 (2019).
pubmed: 30814732
pmcid: 6546093
Berga-Bolanos, R., Alberdi, M., Buxade, M., Aramburu, J. & Lopez-Rodriguez, C. NFAT5 induction by the pre-T-cell receptor serves as a selective survival signal in T-lymphocyte development. Proc. Natl Acad. Sci. USA 110, 16091–16096 (2013).
pubmed: 24043824
pmcid: 3791764
Tirosh, I. et al. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science 352, 189–196 (2016).
pubmed: 27124452
pmcid: 4944528
Scott, A. C. et al. TOX is a critical regulator of tumour-specific T cell differentiation. Nature 571, 270–274 (2019).
pubmed: 31207604
pmcid: 7698992
Chamoto, K., Yaguchi, T., Tajima, M. & Honjo, T. Insights from a 30-year journey: function, regulation and therapeutic modulation of PD1. Nat. Rev. Immunol. https://doi.org/10.1038/s41577-023-00867-9 , (2023).
Wherry, E. J. et al. Molecular signature of CD8
pubmed: 17950003
Charmoy, M., Wyss, T., Delorenzi, M. & Held, W. PD-1
pubmed: 34496259
Kumar, R. et al. NFAT5, which protects against hypertonicity, is activated by that stress via structuring of its intrinsically disordered domain. Proc. Natl Acad. Sci. USA 117, 20292–20297 (2020).
pubmed: 32747529
pmcid: 7443939
Drews-Elger, K., Ortells, M. C., Rao, A., Lopez-Rodriguez, C. & Aramburu, J. The transcription factor NFAT5 is required for cyclin expression and cell cycle progression in cells exposed to hypertonic stress. PLoS ONE 4, e5245 (2009).
pubmed: 19381288
pmcid: 2667631
Conzelmann, A., Corthesy, P., Cianfriglia, M., Silva, A. & Nabholz, M. Hybrids between rat lymphoma and mouse T cells with inducible cytolytic activity. Nature 298, 170–172 (1982).
pubmed: 6979720
Verdeil, G., Chaix, J., Schmitt-Verhulst, A. M. & Auphan-Anezin, N. Temporal cross-talk between TCR and STAT signals for CD8 T cell effector differentiation. Eur. J. Immunol. 36, 3090–3100 (2006).
pubmed: 17111352
Patro, R., Duggal, G., Love, M. I., Irizarry, R. A. & Kingsford, C. Salmon provides fast and bias-aware quantification of transcript expression. Nat. Methods 14, 417–419 (2017).
pubmed: 28263959
pmcid: 5600148
Hunt, S. E. et al. Ensembl variation resources. Database 2018, bay119 (2018).
pubmed: 30576484
pmcid: 6310513
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
pubmed: 25516281
pmcid: 4302049
Soneson, C., Love, M. I. & Robinson, M. D. Differential analyses for RNA-seq: transcript-level estimates improve gene-level inferences. F1000Res 4, 1521 (2015).
pubmed: 26925227
Aibar, S. et al. SCENIC: single-cell regulatory network inference and clustering. Nat. Methods 14, 1083–1086 (2017).
pubmed: 28991892
pmcid: 5937676
Huynh-Thu, V. A., Irrthum, A., Wehenkel, L. & Geurts, P. Inferring regulatory networks from expression data using tree-based methods. PLoS ONE 5, e12776 (2010).
pubmed: 20927193
pmcid: 2946910
Herrmann, C., Van de Sande, B., Potier, D. & Aerts, S. i-cisTarget: an integrative genomics method for the prediction of regulatory features and cis-regulatory modules. Nucleic Acids Res. 40, e114 (2012).
pubmed: 22718975
pmcid: 3424583
Imrichova, H., Hulselmans, G., Atak, Z. K., Potier, D. & Aerts, S. i-cisTarget 2015 update: generalized cis-regulatory enrichment analysis in human, mouse and fly. Nucleic Acids Res. 43, W57–W64 (2015).
pubmed: 25925574
pmcid: 4489282
Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573–3587 (2021).
pubmed: 34062119
pmcid: 8238499
Wu, T. et al. clusterProfiler 4.0: a universal enrichment tool for interpreting omics data. Innov. 2, 100141 (2021).
Andreatta, M. & Carmona, S. J. UCell: robust and scalable single-cell gene signature scoring. Comput Struct. Biotechnol. J. 19, 3796–3798 (2021).
pubmed: 34285779
pmcid: 8271111