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These chemical modifications function as rapid and reversible regulators that link antigenic stimulation, metabolic availability, and inflammatory cues to the transcriptional and chromatin programs that define CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell fate. Core PTM classes\u2014including phosphorylation, ubiquitination, acetylation, methylation, and glycosylation\u2014precisely tune signaling thresholds, cytotoxic commitment, and memory formation, while emerging metabolism\u2010responsive modifications such as lactylation directly connect nutrient flux to functional fitness. In solid tumors, chronic antigen exposure, hypoxia, nutrient restriction, and lactate accumulation profoundly remodel these modification networks, stabilizing dysfunction\u2010associated states, impairing metabolic flexibility, and diminishing cytotoxic capacity. This review integrates current mechanistic understanding of how major PTM pathways coordinate the lifecycle of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells\u2014from initial activation to effector acquisition, memory establishment, dysfunction, and exhaustion. We further discuss how the tumor microenvironment reprograms PTM landscapes to reinforce dysfunction and promote immune escape. Finally, we highlight the challenges and future directions in deciphering and targeting PTMs in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Future efforts to manipulate PTMs hold significant potential to improve cancer immunotherapies by restoring the antitumor efficacy of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells within the tumor microenvironment.\n                  <\/jats:p>","DOI":"10.1002\/advs.74807","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T10:25:58Z","timestamp":1773311158000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Post\u2010Translational Regulation of CD8\n                    <sup>+<\/sup>\n                    T Cell Fate and Dysfunction in Tumor Immunity"],"prefix":"10.1002","volume":"13","author":[{"given":"Zihao","family":"Zhou","sequence":"first","affiliation":[{"name":"Stomatological Hospital, School of Stomatology Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Chen","sequence":"additional","affiliation":[{"name":"Stomatological Hospital, School of Stomatology Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Li","sequence":"additional","affiliation":[{"name":"Stomatological Hospital, School of Stomatology Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiyan","family":"Zou","sequence":"additional","affiliation":[{"name":"Stomatological Hospital, School of Stomatology Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfan","family":"Lin","sequence":"additional","affiliation":[{"name":"Stomatological Hospital, School of Stomatology Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Lin","sequence":"additional","affiliation":[{"name":"Stomatological Hospital, School of Stomatology Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyao","family":"Feng","sequence":"additional","affiliation":[{"name":"Stomatological Hospital, School of Stomatology Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4770-8877","authenticated-orcid":false,"given":"Xinyuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Stomatological Hospital, School of Stomatology Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9814-6945","authenticated-orcid":false,"given":"Li","family":"Cui","sequence":"additional","affiliation":[{"name":"Stomatological Hospital, School of Stomatology Southern Medical University  Guangzhou Guangdong China"},{"name":"School of Dentistry University of California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010021\u201000537\u20108"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a038661"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.146"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967\u2010023\u201004775\u20103"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3307"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.09.006"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.04.014"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22367"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2013.10.001"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.09.014"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19030819"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology12091163"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1503018"},{"issue":"3","key":"e_1_2_11_15_1","first-page":"107","article-title":"Regulation of T Cell Receptor Complex\u2010Mediated Signaling by Ubiquitin and Ubiquitin\u2010Like Modifications","volume":"3","author":"Friend S. 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