Transgelin 2 guards T cell lipid metabolism and antitumour function.


Journal

Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462

Informations de publication

Date de publication:
23 Oct 2024
Historique:
received: 29 11 2023
accepted: 18 09 2024
medline: 24 10 2024
pubmed: 24 10 2024
entrez: 24 10 2024
Statut: aheadofprint

Résumé

Mounting effective immunity against pathogens and tumours relies on the successful metabolic programming of T cells by extracellular fatty acids

Identifiants

pubmed: 39443795
doi: 10.1038/s41586-024-08071-y
pii: 10.1038/s41586-024-08071-y
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer Nature Limited.

Références

Lim, S. A., Su, W., Chapman, N. M. & Chi, H. Lipid metabolism in T cell signaling and function. Nat. Chem. Biol. 18, 470–481 (2022).
pubmed: 35484263 pmcid: 11103273 doi: 10.1038/s41589-022-01017-3
Zhang, Y. et al. Enhancing CD8
pubmed: 28898698 pmcid: 5751418 doi: 10.1016/j.ccell.2017.08.004
Nava Lauson, C. B. et al. Linoleic acid potentiates CD8
pubmed: 36898381 doi: 10.1016/j.cmet.2023.02.013
Pan, Y. et al. Survival of tissue-resident memory T cells requires exogenous lipid uptake and metabolism. Nature 543, 252–256 (2017).
pubmed: 28219080 pmcid: 5509051 doi: 10.1038/nature21379
Lin, R. et al. Fatty acid oxidation controls CD8
pubmed: 32075801 doi: 10.1158/2326-6066.CIR-19-0702
Reinfeld, B. I. et al. Cell-programmed nutrient partitioning in the tumour microenvironment. Nature 593, 282–288 (2021).
pubmed: 33828302 pmcid: 8122068 doi: 10.1038/s41586-021-03442-1
Long, L. et al. CRISPR screens unveil signal hubs for nutrient licensing of T cell immunity. Nature 600, 308–313 (2021).
pubmed: 34795452 pmcid: 8887674 doi: 10.1038/s41586-021-04109-7
Fox, C. J., Hammerman, P. S. & Thompson, C. B. Fuel feeds function: energy metabolism and the T-cell response. Nat. Rev. Immunol. 5, 844–852 (2005).
pubmed: 16239903 doi: 10.1038/nri1710
Byersdorfer, C. A. et al. Effector T cells require fatty acid metabolism during murine graft-versus-host disease. Blood 122, 3230–3237 (2013).
pubmed: 24046012 pmcid: 3814737 doi: 10.1182/blood-2013-04-495515
Pearce, E. L. et al. Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature 460, 103–107 (2009).
pubmed: 19494812 pmcid: 2803086 doi: 10.1038/nature08097
Jin, R. et al. Role of FABP5 in T cell lipid metabolism and function in the tumor microenvironment. Cancers 15, 657 (2023).
pubmed: 36765614 pmcid: 9913835 doi: 10.3390/cancers15030657
Liu, F. et al. Identification of FABP5 as an immunometabolic marker in human hepatocellular carcinoma. J. Immunother. Cancer 8, e000501 (2020).
pubmed: 32611686 pmcid: 7332195 doi: 10.1136/jitc-2019-000501
Matulonis, U. A. et al. Ovarian cancer. Nat. Rev. Dis. Primers 2, 16061 (2016).
pubmed: 27558151 pmcid: 7290868 doi: 10.1038/nrdp.2016.61
Matulonis, U. A. et al. Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study. Ann. Oncol. 30, 1080–1087 (2019).
pubmed: 31046082 doi: 10.1093/annonc/mdz135
Kandalaft, L. E., Dangaj Laniti, D. & Coukos, G. Immunobiology of high-grade serous ovarian cancer: lessons for clinical translation. Nat. Rev. Cancer 22, 640–656 (2022).
pubmed: 36109621 doi: 10.1038/s41568-022-00503-z
Song, M. et al. IRE1α–XBP1 controls T cell function in ovarian cancer by regulating mitochondrial activity. Nature 562, 423–428 (2018).
pubmed: 30305738 pmcid: 6237282 doi: 10.1038/s41586-018-0597-x
Cao, Y. et al. ER stress-induced mediator C/EBP homologous protein thwarts effector T cell activity in tumors through T-bet repression. Nat. Commun. 10, 1280 (2019).
pubmed: 30894532 pmcid: 6426975 doi: 10.1038/s41467-019-09263-1
Anadon, C. M. et al. Ovarian cancer immunogenicity is governed by a narrow subset of progenitor tissue-resident memory T cells. Cancer Cell 40, 545–557.e13 (2022).
pubmed: 35427494 pmcid: 9096229 doi: 10.1016/j.ccell.2022.03.008
Bowtell, D. D. The genesis and evolution of high-grade serous ovarian cancer. Nat. Rev. Cancer 10, 803–808 (2010).
pubmed: 20944665 doi: 10.1038/nrc2946
Digre, A. & Lindskog, C. The Human Protein Atlas—spatial localization of the human proteome in health and disease. Protein Sci. 30, 218–233 (2021).
pubmed: 33146890 doi: 10.1002/pro.3987
Conejo-Garcia, J. R. et al. Tumor-infiltrating dendritic cell precursors recruited by a β-defensin contribute to vasculogenesis under the influence of Vegf-A. Nat. Med. 10, 950–958 (2004).
pubmed: 15334073 doi: 10.1038/nm1097
Chae, C. S. et al. Tumor-derived lysophosphatidic acid blunts protective type-I interferon responses in ovarian cancer. Cancer Discov. 12, 1904–1921 (2022).
pubmed: 35552618 pmcid: 9357054 doi: 10.1158/2159-8290.CD-21-1181
Cubillos-Ruiz, J. R. et al. Reprogramming tumor-associated dendritic cells in vivo using miRNA mimetics triggers protective immunity against ovarian cancer. Cancer Res. 72, 1683–1693 (2012).
pubmed: 22307839 pmcid: 3319850 doi: 10.1158/0008-5472.CAN-11-3160
Cubillos-Ruiz, J. R. et al. Polyethylenimine-based siRNA nanocomplexes reprogram tumor-associated dendritic cells via TLR5 to elicit therapeutic antitumor immunity. J. Clin. Invest. 119, 2231–2244 (2009).
pubmed: 19620771 pmcid: 2719935
Cubillos-Ruiz, J. R. et al. ER stress sensor XBP1 controls anti-tumor immunity by disrupting dendritic cell homeostasis. Cell 161, 1527–1538 (2015).
pubmed: 26073941 pmcid: 4580135 doi: 10.1016/j.cell.2015.05.025
Scarlett, U. K. et al. Ovarian cancer progression is controlled by phenotypic changes in dendritic cells. J. Exp. Med. 209, 495–506 (2012).
pubmed: 22351930 pmcid: 3302234 doi: 10.1084/jem.20111413
Szklarczyk, D. et al. The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res. 49, D605–D612 (2021).
pubmed: 33237311 doi: 10.1093/nar/gkaa1074
Wan, C. H. et al. Panorama of ancient metazoan macromolecular complexes. Nature 525, 339–344 (2015).
pubmed: 26344197 pmcid: 5036527 doi: 10.1038/nature14877
Yin, L. M., Ulloa, L. & Yang, Y. Q. Transgelin-2: biochemical and clinical implications in cancer and asthma. Trends Biochem. Sci. 44, 885–896 (2019).
pubmed: 31256982 doi: 10.1016/j.tibs.2019.05.004
Jo, S., Kim, H. R., Mun, Y. & Jun, C. D. Transgelin-2 in immunity: Its implication in cell therapy. J. Leukoc. Biol. 104, 903–910 (2018).
pubmed: 29749649 doi: 10.1002/JLB.MR1117-470R
Ortega, F. J. et al. Cytoskeletal transgelin 2 contributes to gender-dependent adipose tissue expandability and immune function. FASEB J. 33, 9656–9671 (2019).
pubmed: 31145872 doi: 10.1096/fj.201900479R
Na, B. R. et al. TAGLN2 regulates T cell activation by stabilizing the actin cytoskeleton at the immunological synapse. J. Cell Biol. 209, 143–162 (2015).
pubmed: 25869671 pmcid: 4395477 doi: 10.1083/jcb.201407130
Armstrong, E. H., Goswami, D., Griffin, P. R., Noy, N. & Ortlund, E. A. Structural basis for ligand regulation of the fatty acid-binding protein 5, peroxisome proliferator-activated receptor β/δ (FABP5-PPARβ/δ) signaling pathway. J. Biol. Chem. 289, 14941–14954 (2014).
pubmed: 24692551 pmcid: 4031543 doi: 10.1074/jbc.M113.514646
Furuhashi, M. & Hotamisligil, G. S. Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets. Nat. Rev. Drug Discovery 7, 489–503 (2008).
pubmed: 18511927 doi: 10.1038/nrd2589
Fung, H. Y., Teryek, M., Lemenze, A. D. & Bergsbaken, T. CD103 fate mapping reveals that intestinal CD103
pubmed: 36332012 pmcid: 9901738 doi: 10.1126/sciimmunol.abl9925
Giles, J. R. et al. Shared and distinct biological circuits in effector, memory and exhausted CD8
pubmed: 36271148 pmcid: 10408358 doi: 10.1038/s41590-022-01338-4
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 doi: 10.1126/science.aad0501
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 doi: 10.1038/s41586-019-1324-y
Hetz, C., Zhang, K. & Kaufman, R. J. Mechanisms, regulation and functions of the unfolded protein response. Nat. Rev. Mol. Cell Biol. 21, 421–438 (2020).
pubmed: 32457508 pmcid: 8867924 doi: 10.1038/s41580-020-0250-z
Chen, X. & Cubillos-Ruiz, J. R. Endoplasmic reticulum stress signals in the tumour and its microenvironment. Nat. Rev. Cancer 21, 71–88 (2021).
pubmed: 33214692 doi: 10.1038/s41568-020-00312-2
Yoshida, H., Matsui, T., Yamamoto, A., Okada, T. & Mori, K. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 107, 881–891 (2001).
pubmed: 11779464 doi: 10.1016/S0092-8674(01)00611-0
Logue, S. E. et al. Inhibition of IRE1 RNase activity modulates the tumor cell secretome and enhances response to chemotherapy. Nat. Commun. 9, 3267 (2018).
pubmed: 30111846 pmcid: 6093931 doi: 10.1038/s41467-018-05763-8
Morita, S. et al. Targeting ABL-IRE1α signaling spares ER-stressed pancreatic β cells to reverse autoimmune diabetes. Cell Metab. 25, 1207 (2017).
pubmed: 28467938 doi: 10.1016/j.cmet.2017.04.026
Di Conza, G., Ho, P. C., Cubillos-Ruiz, J. R. & Huang, S. C. Control of immune cell function by the unfolded protein response. Nat. Rev. Immunol. 23, 546–562 (2023).
pubmed: 36755160 doi: 10.1038/s41577-023-00838-0
Kim, H. R. et al. An essential role for TAGLN2 in phagocytosis of lipopolysaccharide-activated macrophages. Sci. Rep. 7, 8731 (2017).
pubmed: 28821818 pmcid: 5562783 doi: 10.1038/s41598-017-09144-x
Iyer, S. et al. Genetically defined syngeneic mouse models of ovarian cancer as tools for the discovery of combination immunotherapy. Cancer Discov. 11, 384–407 (2021).
pubmed: 33158843 doi: 10.1158/2159-8290.CD-20-0818
Zhang, K. Y. et al. Longitudinal single-cell RNA-seq analysis reveals stress-promoted chemoresistance in metastatic ovarian cancer. Sci. Adv. 8, eabm1831 (2022).
pubmed: 35196078 pmcid: 8865800 doi: 10.1126/sciadv.abm1831
Snaebjornsson, M. T., Janaki-Raman, S. & Schulze, A. Greasing the wheels of the cancer machine: the role of lipid metabolism in cancer. Cell Metab. 31, 62–76 (2020).
pubmed: 31813823 doi: 10.1016/j.cmet.2019.11.010
Shender, V. O. et al. Proteome–metabolome profiling of ovarian cancer ascites reveals novel components involved in intercellular communication. Mol. Cell. Proteomics 13, 3558–3571 (2014).
pubmed: 25271300 pmcid: 4256505 doi: 10.1074/mcp.M114.041194
Perales-Puchalt, A. et al. Follicle-stimulating hormone receptor is expressed by most ovarian cancer subtypes and is a safe and effective immunotherapeutic target. Clin. Cancer Res. 23, 441–453 (2017).
pubmed: 27435394 doi: 10.1158/1078-0432.CCR-16-0492
Paffenholz, S. V. et al. Senescence induction dictates response to chemo- and immunotherapy in preclinical models of ovarian cancer. Proc. Natl Acad. Sci. USA 119, e2117754119 (2022).
pubmed: 35082152 pmcid: 8812522 doi: 10.1073/pnas.2117754119
Pramanik, J. et al. Genome-wide analyses reveal the IRE1a-XBP1 pathway promotes T helper cell differentiation by resolving secretory stress and accelerating proliferation. Genome Med. 10, 76 (2018).
Bogdan, D. M. et al. FABP5 deletion in nociceptors augments endocannabinoid signaling and suppresses TRPV1 sensitization and inflammatory pain. Sci. Rep. 12, 9241 (2022).
pubmed: 35655086 pmcid: 9163147 doi: 10.1038/s41598-022-13284-0
Lee, A. H., Scapa, E. F., Cohen, D. E. & Glimcher, L. H. Regulation of hepatic lipogenesis by the transcription factor XBP1. Science 320, 1492–1496 (2008).
pubmed: 18556558 pmcid: 3620093 doi: 10.1126/science.1158042
Iwawaki, T., Akai, R., Yamanaka, S. & Kohno, K. Function of IRE1 alpha in the placenta is essential for placental development and embryonic viability. Proc. Natl Acad. Sci. USA 106, 16657–16662 (2009).
pubmed: 19805353 pmcid: 2757843 doi: 10.1073/pnas.0903775106
Chopra, S. et al. IRE1α–XBP1 signaling in leukocytes controls prostaglandin biosynthesis and pain. Science 365, eaau6499 (2019).
pubmed: 31320508 doi: 10.1126/science.aau6499
de Boer, J. et al. Transgenic mice with hematopoietic and lymphoid specific expression of Cre. Eur. J. Immunol. 33, 314–325 (2003).
pubmed: 12548562 doi: 10.1002/immu.200310005
Roby, K. F. et al. Development of a syngeneic mouse model for events related to ovarian cancer. Carcinogenesis 21, 585–591 (2000).
pubmed: 10753190 doi: 10.1093/carcin/21.4.585
Ichikawa, T. et al. Chemical fixation creates nanoscale clusters on the cell surface by aggregating membrane proteins. Commun. Biol. 5, 487 (2022).
pubmed: 35595960 pmcid: 9122943 doi: 10.1038/s42003-022-03437-2
Bolte, S. & Cordelieres, F. P. A guided tour into subcellular colocalization analysis in light microscopy. J. Microsc. 224, 213–232 (2006).
pubmed: 17210054 doi: 10.1111/j.1365-2818.2006.01706.x
Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573–3587.e29 (2021).
pubmed: 34062119 pmcid: 8238499 doi: 10.1016/j.cell.2021.04.048
Xu, J. et al. Single-cell RNA sequencing reveals the tissue architecture in human high-grade serous ovarian cancer. Clin. Cancer Res. 28, 3590–3602 (2022).
pubmed: 35675036 pmcid: 9662915 doi: 10.1158/1078-0432.CCR-22-0296
Satija, R., Farrell, J. A., Gennert, D., Schier, A. F. & Regev, A. Spatial reconstruction of single-cell gene expression data. Nat. Biotechnol. 33, 495–502 (2015).
pubmed: 25867923 pmcid: 4430369 doi: 10.1038/nbt.3192
Zheng, L. et al. Pan-cancer single-cell landscape of tumor-infiltrating T cells. Science 374, abe6474 (2021).
pubmed: 34914499 doi: 10.1126/science.abe6474
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 doi: 10.1038/s41467-021-23324-4
Chu, Y. et al. Pan-cancer T cell atlas links a cellular stress response state to immunotherapy resistance. Nat. Med. 29, 1550–1562 (2023).
pubmed: 37248301 pmcid: 11421770 doi: 10.1038/s41591-023-02371-y
Khan, O. et al. TOX transcriptionally and epigenetically programs CD8
pubmed: 31207603 pmcid: 6713202 doi: 10.1038/s41586-019-1325-x
Wu, T. et al. clusterProfiler 4.0: a universal enrichment tool for interpreting omics data. Innovation 2, 100141 (2021).
pubmed: 34557778 pmcid: 8454663

Auteurs

Sung-Min Hwang (SM)

Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY, USA.
Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.

Deepika Awasthi (D)

Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY, USA.
Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.

Jieun Jeong (J)

Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Tito A Sandoval (TA)

Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY, USA.
Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.

Chang-Suk Chae (CS)

Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY, USA.
Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
Research Institute, National Cancer Center, Goyang, Republic of Korea.

Yusibeska Ramos (Y)

Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY, USA.

Chen Tan (C)

Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY, USA.
Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.

Matías Marin Falco (M)

Research Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Camilla Salvagno (C)

Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY, USA.
Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.

Alexander Emmanuelli (A)

Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY, USA.
Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
Weill Cornell Graduate School of Medical Sciences, New York, NY, USA.

Ian T McBain (IT)

Weill Cornell Graduate School of Medical Sciences, New York, NY, USA.

Bikash Mishra (B)

Weill Cornell Graduate School of Medical Sciences, New York, NY, USA.
HSS Research Institute and David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY, USA.

Lionel B Ivashkiv (LB)

Weill Cornell Graduate School of Medical Sciences, New York, NY, USA.
HSS Research Institute and David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY, USA.

Dmitriy Zamarin (D)

Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Evelyn Cantillo (E)

Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY, USA.
Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.

Eloise Chapman-Davis (E)

Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY, USA.
Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.

Kevin Holcomb (K)

Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY, USA.
Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.

Diana K Morales (DK)

Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY, USA.

Xiaoqing Yu (X)

Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.

Paulo C Rodriguez (PC)

Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.

Jose R Conejo-Garcia (JR)

Department of Integrated Immunobiology, Duke School of Medicine, Durham, NC, USA.
Duke Cancer Institute, Duke School of Medicine, Durham, NC, USA.

Martin Kaczocha (M)

Department of Anesthesiology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, USA.
Institute of Chemical Biology and Drug Discovery, Stony Brook University, Stony Brook, NY, USA.
Stony Brook University Pain and Analgesia Research Center (SPARC), Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, USA.

Anna Vähärautio (A)

Research Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Foundation for the Finnish Cancer Institute, Helsinki, Finland.

Minkyung Song (M)

Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY, USA.
Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
Departments of Integrative Biotechnology and of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon, Republic of Korea.

Juan R Cubillos-Ruiz (JR)

Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY, USA. jur2016@med.cornell.edu.
Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. jur2016@med.cornell.edu.
Weill Cornell Graduate School of Medical Sciences, New York, NY, USA. jur2016@med.cornell.edu.

Classifications MeSH