{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:08:26Z","timestamp":1788786506794,"version":"build-2803163510"},"reference-count":155,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007847","name":"Natural Science Foundation of Jilin Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009991","name":"Department of Finance of Jilin Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009991","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Aminoacyl-tRNA synthetases (aaRSs) generate the aminoacyl-tRNA pool required for protein synthesis, yet selected family members also participate in nutrient sensing, stress adaptation, metabolite-dependent protein modification and extracellular immune communication. This dual biology creates a recurrent interpretive problem in cancer: an aaRS signal can reflect canonical translational demand in tumor cells, a mitochondrial program specific to immune cells, protein modification driven by lactate or amino acids, an interferon-responsive state, a secreted ligand or extracellular vesicle cargo. This review provides a mechanistic, critically appraised synthesis rather than a catalog of the aaRS family. We reconnect aminoacylation, codon-dependent translation and aaRS-specific translational stress with tumor biology and then apply a source-resolved framework based on cellular source, molecular form, localization, receiving pathway and immune output. Mechanistic strength and clinical maturity are graded independently, with direct evidence of immune function recorded separately. Representative mechanisms include substrate-specific AARS1\/AARS2 lactylation, context-dependent LARS1 programs driven by codon demand, LARS2-dependent mitochondrial translation in tumor-infiltrating regulatory T cells (TI-Tregs) and regulatory B cells (Bregs), activation of Toll-like receptor 2\/6 (TLR2\/6) by the unique domain embedded in CARS1 (UNE-C1), WARS1 tryptophanylation intrinsic to CD8+ T cells, KARS1 and GARS1 circuits that depend on molecular form, and additional QARS1, MARS1, RARS1 and VARS1 mechanisms. Several modules show strong preclinical immune causality and human association, but none has prospective clinical validation in treated patients. aaRS-informed biomarkers and therapeutic targeting should therefore be developed as complementary, context-dependent strategies.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1922154","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T12:16:50Z","timestamp":1788783410000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Aminoacyl-tRNA synthetases in tumor immunity: canonical translation, source-resolved immune circuits and therapeutic opportunities"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhipeng","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University","place":["Changchun, Jilin, 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