{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T02:25:27Z","timestamp":1787192727274,"version":"build-2736575974"},"reference-count":74,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32503237"],"award-info":[{"award-number":["32503237"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024M750926"],"award-info":[{"award-number":["2024M750926"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The programmed death ligand 1\/programmed cell death 1 (PD-L1\/PD-1) serves as a critical immune checkpoint in T cell\u2013mediated immune responses, playing a central role in maintaining peripheral immune tolerance and homeostasis. Although early vertebrates lack a PD-1 homolog and they retain PD-L1, the functional significance and regulatory mechanisms of PD-L1 in T-cell immunity in these species remain poorly understood. In this study, using Nile tilapia (Oreochromis niloticus) as a teleost model, we systematically investigated the immunosuppressive role of PD-L1 in T-cell immunity. PD-L1 was widely expressed in various lymphoid tissues, and both its mRNA and protein levels were significantly upregulated following T-cell activation induced by mAbs against CD3\/CD28 and Edwardsiella piscicida infection. Functional analyses demonstrated that exogenous PD-L1 treatment markedly suppressed T-cell activation and promoted activation-induced apoptosis. Moreover, PD-L1 treatment significantly impaired T-cell proliferation, effector cytokine production, and cytotoxic activity, ultimately compromising antibacterial immune defense. Mechanistically, activated tilapia T cells exhibited enhanced de novo fatty acid synthesis, whereas PD-L1 disrupted this metabolic reprogramming by inhibiting key enzymatic activities and reducing acetyl-CoA accumulation, ultimately leading to impaired T-cell function. Notably, restoration of fatty acid synthesis effectively reversed the PD-L1\u2013induced immunosuppressive effects on tilapia T cells. In summary, this study reveals a previously unrecognized mechanism by which PD-L1 suppresses T-cell immunity in an early vertebrate through modulation of lipid metabolism. These findings highlight the essential role of metabolism regulation in immune checkpoint signaling and provide new evolutionary insights into the maintenance of T-cell homeostasis.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag236","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T02:10:32Z","timestamp":1787191832000},"source":"Crossref","is-referenced-by-count":0,"title":["PD-L1 restrains T-cell immunity in Nile tilapia by suppressing activation-induced fatty acid synthesis"],"prefix":"10.1093","volume":"215","author":[{"given":"Jiansong","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunming","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqi","family":"Tang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialong","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University , Shanghai,","place":["China"]},{"name":"Qingdao Marine Science and Technology Center, Laboratory for Marine Biology and Biotechnology , Qingdao,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2253-8181","authenticated-orcid":false,"given":"Xiumei","family":"Wei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"2026081922102604700_vkag236-B1","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.3390\/ijms25021274","article-title":"The role of the CD28 family receptors in T-cell immunomodulation","volume":"25","author":"Ciesielska-Figlon","year":"2024","journal-title":"Int J Mol Sci"},{"key":"2026081922102604700_vkag236-B2","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/s41392-021-00823-w","article-title":"T cell receptor (TCR) signaling in health and disease","volume":"6","author":"Shah","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"2026081922102604700_vkag236-B3","doi-asserted-by":"crossref","first-page":"977394","DOI":"10.3389\/fimmu.2022.977394","article-title":"T-cell exhaustion in immune-mediated inflammatory diseases: new implications for immunotherapy","volume":"13","author":"Gao","year":"2022","journal-title":"Front Immunol"},{"key":"2026081922102604700_vkag236-B4","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1038\/s41590-019-0512-0","article-title":"Inhibitory receptors and ligands beyond PD-1, PD-L1 and CTLA-4: breakthroughs or backups","volume":"20","author":"Andrews","year":"2019","journal-title":"Nat Immunol"},{"key":"2026081922102604700_vkag236-B5","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1053\/j.gastro.2017.06.017","article-title":"Antibodies against immune checkpoint molecules restore functions of tumor-infiltrating T cells in hepatocellular carcinomas","volume":"153","author":"Zhou","year":"2017","journal-title":"Gastroenterology"},{"key":"2026081922102604700_vkag236-B6","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1146\/annurev.immunol.26.021607.090331","article-title":"PD-1 and its ligands in tolerance and immunity","volume":"26","author":"Keir","year":"2008","journal-title":"Annu Rev Immunol"},{"key":"2026081922102604700_vkag236-B7","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.immuni.2007.05.016","article-title":"Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses","volume":"27","author":"Butte","year":"2007","journal-title":"Immunity"},{"key":"2026081922102604700_vkag236-B8","doi-asserted-by":"crossref","first-page":"5029","DOI":"10.7150\/thno.107418","article-title":"PD-1 activation mitigates lupus nephritis by suppressing hyperactive and heterogeneous PD-1(+)CD8(+) T cells","volume":"15","author":"Deng","year":"2025","journal-title":"Theranostics"},{"key":"2026081922102604700_vkag236-B9","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.1038\/sj.emboj.7601146","article-title":"T-cell tolerance or function is determined by combinatorial costimulatory signals","volume":"25","author":"Nurieva","year":"2006","journal-title":"EMBO J"},{"key":"2026081922102604700_vkag236-B10","doi-asserted-by":"crossref","first-page":"945","DOI":"10.4049\/jimmunol.173.2.945","article-title":"SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation","volume":"173","author":"Chemnitz","year":"2004","journal-title":"J Immunol"},{"key":"2026081922102604700_vkag236-B11","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S1074-7613(00)80089-8","article-title":"Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor","volume":"11","author":"Nishimura","year":"1999","journal-title":"Immunity"},{"key":"2026081922102604700_vkag236-B12","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1126\/science.291.5502.319","article-title":"Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice","volume":"291","author":"Nishimura","year":"2001","journal-title":"Science"},{"key":"2026081922102604700_vkag236-B13","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.1172\/JCI62860","article-title":"Viral acute lower respiratory infections impair CD8+ T cells through PD-1","volume":"122","author":"Erickson","year":"2012","journal-title":"J Clin Invest"},{"key":"2026081922102604700_vkag236-B14","doi-asserted-by":"crossref","first-page":"5811","DOI":"10.1182\/blood-2009-02-203141","article-title":"PD-1 on dendritic cells impedes innate immunity against bacterial infection","volume":"113","author":"Yao","year":"2009","journal-title":"Blood"},{"key":"2026081922102604700_vkag236-B15","doi-asserted-by":"crossref","first-page":"13866","DOI":"10.1073\/pnas.231486598","article-title":"PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine","volume":"98","author":"Okazaki","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026081922102604700_vkag236-B16","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2022-005845","article-title":"Negative intracellular regulators of T-cell receptor (TCR) signaling as potential antitumor immunotherapy targets","volume":"11","author":"Laletin","year":"2023","journal-title":"J Immunother Cancer"},{"key":"2026081922102604700_vkag236-B17","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1111\/j.1600-065X.2008.00760.x","article-title":"SHP-1 and SHP-2 in T cells: two phosphatases functioning at many levels","volume":"228","author":"Lorenz","year":"2009","journal-title":"Immunol Rev"},{"key":"2026081922102604700_vkag236-B18","doi-asserted-by":"crossref","first-page":"9543","DOI":"10.1128\/MCB.25.21.9543-9553.2005","article-title":"CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms","volume":"25","author":"Parry","year":"2005","journal-title":"Mol Cell Biol"},{"key":"2026081922102604700_vkag236-B19","doi-asserted-by":"crossref","first-page":"3561","DOI":"10.1002\/eji.200526347","article-title":"PD-L2: PD-1 involvement in T cell proliferation, cytokine production, and integrin-mediated adhesion","volume":"35","author":"Saunders","year":"2005","journal-title":"Eur J Immunol"},{"key":"2026081922102604700_vkag236-B20","doi-asserted-by":"crossref","first-page":"3434","DOI":"10.7150\/jca.77619","article-title":"Clinical implications of the interaction between PD-1\/PD-L1 and PI3K\/AKT\/mTOR pathway in progression and treatment of non-small cell lung cancer","volume":"13","author":"Quan","year":"2022","journal-title":"J Cancer"},{"key":"2026081922102604700_vkag236-B21","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1111\/imm.13575","article-title":"Metabolic plasticity and regulation of T cell exhaustion","volume":"167","author":"Li","year":"2022","journal-title":"Immunology"},{"key":"2026081922102604700_vkag236-B22","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s12943-025-02407-6","article-title":"Metabolic checkpoints in immune cell reprogramming: rewiring immunometabolism for cancer therapy","volume":"24","author":"Lv","year":"2025","journal-title":"Mol Cancer"},{"key":"2026081922102604700_vkag236-B23","doi-asserted-by":"crossref","first-page":"840610","DOI":"10.3389\/fimmu.2022.840610","article-title":"T cell metabolism in infection","volume":"13","author":"Wik","year":"2022","journal-title":"Front Immunol"},{"key":"2026081922102604700_vkag236-B24","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1038\/nm.3704","article-title":"De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells","volume":"20","author":"Berod","year":"2014","journal-title":"Nat Med"},{"key":"2026081922102604700_vkag236-B25","doi-asserted-by":"crossref","first-page":"102111","DOI":"10.1016\/j.molmet.2025.102111","article-title":"ACC1 is a dual metabolic-epigenetic regulator of Treg stability and immune tolerance","volume":"94","author":"St\u00fcve","year":"2025","journal-title":"Mol Metab"},{"key":"2026081922102604700_vkag236-B26","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.molimm.2008.10.007","article-title":"The B7 family of immunoregulatory receptors: a comparative and evolutionary perspective","volume":"46","author":"Hansen","year":"2009","journal-title":"Mol Immunol"},{"key":"2026081922102604700_vkag236-B27","doi-asserted-by":"crossref","first-page":"6799","DOI":"10.4049\/jimmunol.0803371","article-title":"Teleost B7 expressed on monocytes regulates T cell responses","volume":"182","author":"Sugamata","year":"2009","journal-title":"J Immunol"},{"key":"2026081922102604700_vkag236-B28","doi-asserted-by":"crossref","first-page":"2767","DOI":"10.4049\/jimmunol.1701051","article-title":"Teleost basophils have IgM-dependent and dual Ig-independent degranulation systems","volume":"200","author":"Odaka","year":"2018","journal-title":"J Immunol"},{"key":"2026081922102604700_vkag236-B29","doi-asserted-by":"crossref","first-page":"816","DOI":"10.4049\/jimmunol.2300217","article-title":"PD-L1\/BTLA checkpoint axis exploited for bacterial immune escape by restraining CD8+ T cell-initiated adaptive immunity in zebrafish","volume":"211","author":"Hu","year":"2023","journal-title":"J Immunol"},{"key":"2026081922102604700_vkag236-B30","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.4049\/jimmunol.2300251","article-title":"Hyperosmotic stress induces inflammation and excessive Th17 response to blunt T-cell immunity in tilapia","volume":"212","author":"Zhang","year":"2024","journal-title":"J Immunol"},{"key":"2026081922102604700_vkag236-B31","doi-asserted-by":"crossref","first-page":"e1010913","DOI":"10.1371\/journal.ppat.1010913","article-title":"IL-2-mTORC1 signaling coordinates the STAT1\/T-bet axis to ensure Th1 cell differentiation and anti-bacterial immune response in fish","volume":"18","author":"Ai","year":"2022","journal-title":"PLoS Pathog"},{"key":"2026081922102604700_vkag236-B32","doi-asserted-by":"crossref","first-page":"102843","DOI":"10.1016\/j.jbc.2022.102843","article-title":"TGF-\u03b21 suppresses the T-cell response in teleost fish by initiating Smad3- and Foxp3-mediated transcriptional networks","volume":"299","author":"Zhang","year":"2023","journal-title":"J Biol Chem"},{"key":"2026081922102604700_vkag236-B33","doi-asserted-by":"crossref","first-page":"e2201164","DOI":"10.1002\/advs.202201164","article-title":"Glutamine metabolism underlies the functional similarity of T cells between Nile tilapia and tetrapod","volume":"10","author":"Li","year":"2023","journal-title":"Adv Sci (Weinh)"},{"key":"2026081922102604700_vkag236-B34","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.4049\/jimmunol.1900008","article-title":"Ancestral T cells in fish require mTORC1-coupled immune signals and metabolic programming for proper activation and function","volume":"203","author":"Wei","year":"2019","journal-title":"J Immunol"},{"key":"2026081922102604700_vkag236-B35","doi-asserted-by":"crossref","first-page":"569","DOI":"10.4049\/jimmunol.1901065","article-title":"Ca(2+)-calcineurin axis-controlled NFAT nuclear translocation is crucial for optimal T cell immunity in an early vertebrate","volume":"204","author":"Wei","year":"2020","journal-title":"J Immunol"},{"key":"2026081922102604700_vkag236-B36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0171-9335(99)80002-8","article-title":"Brefeldin A (BFA) disrupts the organization of the microtubule and the actin cytoskeletons","volume":"78","author":"Alvarez","year":"1999","journal-title":"Eur J Cell Biol"},{"key":"2026081922102604700_vkag236-B37","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s12964-020-00564-3","article-title":"The TNF\/TNFR2 signaling pathway is a key regulatory factor in endothelial progenitor cell immunosuppressive effect","volume":"18","author":"Naserian","year":"2020","journal-title":"Cell Commun Signal"},{"key":"2026081922102604700_vkag236-B38","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1667\/RR14173.1","article-title":"Inhibition of fatty acid synthase sensitizes prostate cancer cells to radiotherapy","volume":"184","author":"Rae","year":"2015","journal-title":"Radiat Res"},{"key":"2026081922102604700_vkag236-B39","doi-asserted-by":"crossref","first-page":"109865","DOI":"10.1016\/j.fsi.2024.109865","article-title":"Granzyme B secreted by T cells is involved in anti-bacterial immune response of tilapia","volume":"153","author":"Cao","year":"2024","journal-title":"Fish Shellfish Immunol"},{"key":"2026081922102604700_vkag236-B40","doi-asserted-by":"crossref","first-page":"109515","DOI":"10.1016\/j.fsi.2024.109515","article-title":"Inducible IL-2 production and IL-2(+) cell expansion are landmark events for T-cell activation of teleost","volume":"148","author":"Zhang","year":"2024","journal-title":"Fish Shellfish Immunol"},{"key":"2026081922102604700_vkag236-B41","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1016\/j.fsi.2020.09.031","article-title":"S6K1\/S6 axis-regulated lymphocyte activation is important for adaptive immune response of Nile tilapia","volume":"106","author":"Li","year":"2020","journal-title":"Fish Shellfish Immunol"},{"key":"2026081922102604700_vkag236-B42","doi-asserted-by":"crossref","first-page":"109747","DOI":"10.1016\/j.fsi.2024.109747","article-title":"The TAK1\/JNK axis participates in adaptive immunity by promoting lymphocyte activation in Nile tilapia","volume":"151","author":"Wang","year":"2024","journal-title":"Fish Shellfish Immunol"},{"key":"2026081922102604700_vkag236-B43","first-page":"1163","article-title":"A story of kinases and adaptors: the role of Lck, ZAP-70 and LAT in switch panel governing T-cell development and activation","volume":"12","author":"Fern\u00e1ndez-Aguilar","year":"2023","journal-title":"Biology (Basel)"},{"key":"2026081922102604700_vkag236-B44","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.4049\/jimmunol.2300599","article-title":"Fish uses CTLA-4 immune checkpoint to suppress mTORC1-controlled T-cell glycolysis and immunity","volume":"212","author":"Zhang","year":"2024","journal-title":"J Immunol"},{"key":"2026081922102604700_vkag236-B45","doi-asserted-by":"crossref","first-page":"295","DOI":"10.3389\/fimmu.2014.00295","article-title":"Impact of inflammatory cytokines on effector and memory CD8+ T Cells","volume":"5","author":"Kim","year":"2014","journal-title":"Front Immunol"},{"key":"2026081922102604700_vkag236-B46","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1038\/s12276-023-01105-x","article-title":"CD8 T-cell subsets: heterogeneity, functions, and therapeutic potential","volume":"55","author":"Koh","year":"2023","journal-title":"Exp Mol Med"},{"key":"2026081922102604700_vkag236-B47","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41577-019-0203-y","article-title":"Metabolic coordination of T cell quiescence and activation","volume":"20","author":"Chapman","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"2026081922102604700_vkag236-B48","doi-asserted-by":"crossref","first-page":"101006","DOI":"10.1016\/j.plipres.2019.101006","article-title":"ATP-citrate lyase (ACLY) in lipid metabolism and atherosclerosis: an updated review","volume":"77","author":"Feng","year":"2020","journal-title":"Prog Lipid Res"},{"key":"2026081922102604700_vkag236-B49","doi-asserted-by":"crossref","first-page":"706","DOI":"10.3390\/biom12050706","article-title":"Key molecules of fatty acid metabolism in gastric cancer","volume":"12","author":"Li","year":"2022","journal-title":"Biomolecules"},{"key":"2026081922102604700_vkag236-B50","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1007\/s00432-016-2249-6","article-title":"Inhibition of fatty acid synthase suppresses neovascularization via regulating the expression of VEGF-A in glioma","volume":"142","author":"Zhou","year":"2016","journal-title":"J Cancer Res Clin Oncol"},{"key":"2026081922102604700_vkag236-B51","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1189\/jlb.3AB0417-159RR","article-title":"Fatty acid synthase regulates the pathogenicity of Th17 cells","volume":"102","author":"Young","year":"2017","journal-title":"J Leukoc Biol"},{"key":"2026081922102604700_vkag236-B52","doi-asserted-by":"crossref","first-page":"580167","DOI":"10.3389\/fphys.2020.580167","article-title":"Acetate revisited: a key biomolecule at the nexus of metabolism, epigenetics and oncogenesis\u2014part 1: acetyl-CoA, acetogenesis and acyl-CoA short-chain synthetases","volume":"11","author":"Moffett","year":"2020","journal-title":"Front Physiol"},{"key":"2026081922102604700_vkag236-B53","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/s12672-022-00521-1","article-title":"Acetyl-CoA synthetase 2 (ACSS2): a review with a focus on metabolism and tumor development","volume":"13","author":"Ling","year":"2022","journal-title":"Discov Oncol"},{"key":"2026081922102604700_vkag236-B54","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1159\/000464353","article-title":"PD-1\/PD-L1 pathway in breast cancer","volume":"40","author":"Sch\u00fctz","year":"2017","journal-title":"Oncol Res Treat"},{"key":"2026081922102604700_vkag236-B55","doi-asserted-by":"crossref","first-page":"107607","DOI":"10.1016\/j.intimp.2021.107607","article-title":"PD-1\/PD-L1 immune checkpoint blockade-based combinational treatment: immunotherapeutic amplification strategies against colorectal cancer","volume":"96","author":"Chen","year":"2021","journal-title":"Int Immunopharmacol"},{"key":"2026081922102604700_vkag236-B56","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2024-010612","article-title":"Cell-intrinsic PD-L1 signaling drives immunosuppression by myeloid-derived suppressor cells through IL-6\/Jak\/Stat3 in PD-L1-high lung cancer","volume":"13","author":"Jeong","year":"2025","journal-title":"J Immunother Cancer"},{"key":"2026081922102604700_vkag236-B57","doi-asserted-by":"publisher","first-page":"eadl2967","DOI":"10.1126\/sciimmunol.adl2967","article-title":"NK cells restrain cytotoxic CD8(+) T cells in the submandibular gland via PD-1-PD-L1","volume":"9","author":"Borys","year":"2024","journal-title":"Sci Immunol"},{"key":"2026081922102604700_vkag236-B58","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s00262-018-2263-4","article-title":"Inhibitory functions of PD-L1 and PD-L2 in the regulation of anti-tumor immunity in murine tumor microenvironment","volume":"68","author":"Umezu","year":"2019","journal-title":"Cancer Immunol Immunother"},{"key":"2026081922102604700_vkag236-B59","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abd2712","article-title":"Revisiting the PD-1 pathway","volume":"6","author":"Patsoukis","year":"2020","journal-title":"Sci Adv"},{"key":"2026081922102604700_vkag236-B60","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s12943-024-02023-w","article-title":"Regulatory mechanisms of PD-1\/PD-L1 in cancers","volume":"23","author":"Lin","year":"2024","journal-title":"Mol Cancer"},{"key":"2026081922102604700_vkag236-B61","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1158\/2326-6066.CIR-21-0515","article-title":"Reversing T-cell exhaustion in cancer: lessons learned from PD-1\/PD-L1 immune checkpoint blockade","volume":"10","author":"Budimir","year":"2022","journal-title":"Cancer Immunol Res"},{"key":"2026081922102604700_vkag236-B62","doi-asserted-by":"crossref","first-page":"12293","DOI":"10.1073\/pnas.192461099","article-title":"Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade","volume":"99","author":"Iwai","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026081922102604700_vkag236-B63","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.molimm.2015.07.036","article-title":"T cell metabolic reprogramming and plasticity","volume":"68","author":"Slack","year":"2015","journal-title":"Mol Immunol"},{"key":"2026081922102604700_vkag236-B64","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.1016\/j.cmet.2025.09.008","article-title":"Nutrient allocation fuels T cell-mediated immunity","volume":"37","author":"Longo","year":"2025","journal-title":"Cell Metab"},{"key":"2026081922102604700_vkag236-B65","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/ni.2570","article-title":"Sterol regulatory element-binding proteins are essential for the metabolic programming of effector T cells and adaptive immunity","volume":"14","author":"Kidani","year":"2013","journal-title":"Nat Immunol"},{"key":"2026081922102604700_vkag236-B66","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/nature17412","article-title":"Potentiating the antitumour response of CD8(+) T cells by modulating cholesterol metabolism","volume":"531","author":"Yang","year":"2016","journal-title":"Nature"},{"key":"2026081922102604700_vkag236-B67","doi-asserted-by":"crossref","first-page":"3190","DOI":"10.4049\/jimmunol.1302985","article-title":"Regulator of fatty acid metabolism, acetyl coenzyme a carboxylase 1, controls T cell immunity","volume":"192","author":"Lee","year":"2014","journal-title":"J Immunol"},{"key":"2026081922102604700_vkag236-B68","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.immuni.2018.07.018","article-title":"Memory CD8(+) T cells use cell-intrinsic lipolysis to support the metabolic programming necessary for development","volume":"49","author":"O\u2019Sullivan","year":"2018","journal-title":"Immunity"},{"key":"2026081922102604700_vkag236-B69","doi-asserted-by":"crossref","first-page":"6692","DOI":"10.1038\/ncomms7692","article-title":"PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation","volume":"6","author":"Patsoukis","year":"2015","journal-title":"Nat Commun"},{"key":"2026081922102604700_vkag236-B70","doi-asserted-by":"crossref","first-page":"216267","DOI":"10.1016\/j.canlet.2023.216267","article-title":"Lipid metabolism reprogramming of CD8(+) T cell and therapeutic implications in cancer","volume":"567","author":"Wang","year":"2023","journal-title":"Cancer Lett"},{"key":"2026081922102604700_vkag236-B71","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/s41421-019-0130-x","article-title":"Global alteration of T-lymphocyte metabolism by PD-L1 checkpoint involves a block of de novo nucleoside phosphate synthesis","volume":"5","author":"Palaskas","year":"2019","journal-title":"Cell Discov"},{"key":"2026081922102604700_vkag236-B72","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1002\/eji.201243008","article-title":"AMPK\u03b11: a glucose sensor that controls CD8 T-cell memory","volume":"43","author":"Rolf","year":"2013","journal-title":"Eur J Immunol"},{"key":"2026081922102604700_vkag236-B73","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1248\/bpb.b17-00724","article-title":"AMPK-mediated regulation of lipid metabolism by phosphorylation","volume":"41","author":"Wang","year":"2018","journal-title":"Biol Pharm Bull"},{"key":"2026081922102604700_vkag236-B74","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.immuni.2011.09.021","article-title":"The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation","volume":"35","author":"Wang","year":"2011","journal-title":"Immunity"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/215\/8\/vkag236\/70717187\/vkag236.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/215\/8\/vkag236\/70717187\/vkag236.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T02:10:41Z","timestamp":1787191841000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/doi\/10.1093\/jimmun\/vkag236\/8766820"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":74,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8,4]]}},"URL":"https:\/\/doi.org\/10.1093\/jimmun\/vkag236","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,8]]},"published":{"date-parts":[[2026,8]]},"article-number":"vkag236"}}