{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T01:23:49Z","timestamp":1790731429690,"version":"4.1.0"},"reference-count":81,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T00:00:00Z","timestamp":1647388800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["31003A_182470"],"award-info":[{"award-number":["31003A_182470"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000884","name":"Cancer Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000884","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u00a0cells are a key element of the adaptative immune system to protect the organism against infections and malignant cells. During their activation and response, T\u00a0cells undergo different metabolic pathways to support their energetic needs according to their localization and function. However, it has also been recently appreciated that this metabolic reprogramming also directly supports T\u2010cell lineage differentiation. Accordingly, metabolic deficiencies and prolonged stress exposure can impact T\u2010cell differentiation and skew them into an exhausted state. Here, we review how metabolism defines CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell differentiation and function. Moreover, we cover the principal metabolic dysregulation that promotes the exhausted phenotype under tumor or chronic virus conditions. Finally, we summarize recent strategies to reprogram impaired metabolic pathways to promote CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell effector function and survival.\n                  <\/jats:p>","DOI":"10.1002\/eji.202149486","type":"journal-article","created":{"date-parts":[[2022,3,6]],"date-time":"2022-03-06T23:14:11Z","timestamp":1646608451000},"page":"541-549","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Metabolic dynamics instruct CD8\n                    <sup>+<\/sup>\n                    T\u2010cell differentiation and functions"],"prefix":"10.1002","volume":"52","author":[{"given":"Alessio","family":"Bevilacqua","sequence":"first","affiliation":[{"name":"Department of Fundamental Oncology University of Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Fundamental Oncology University of Lausanne  Lausanne Switzerland"},{"name":"Department of Breast and Thyroid Surgery Renmin Hospital of Wuhan University  Wuhan Hubei P. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping\u2010Chih","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Fundamental Oncology University of Lausanne  Lausanne Switzerland"},{"name":"Ludwig Institute for Cancer Research University of Lausanne  Epalinges Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02718"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2016.10.009"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3031"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3307"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2012.01150.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.05.007"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00205-9"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2017.08.033"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2018"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22352"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.12.6869"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-06-096297"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-042617-053019"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.09.021"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1221740110"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.05.035"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.02.010"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)00066-6"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00323-0"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00612-6"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.09.021"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.01.040"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2556"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/imcb.12385"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2687"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI69589"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.12.007"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020067"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5466.675"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.06.002"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.09.031"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200704110"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.10.032"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-041015-055318"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809818106"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-020-00280-9"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3862"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.07.008"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00889-12"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.07.021"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI87324"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.10.038"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.12.021"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0312-6"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19330"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0801497105"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.04.014"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1229620"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4275"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2018.01.005"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.10.020"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7692"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-019-0628-7"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13988"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.08.012"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.c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