{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T09:55:16Z","timestamp":1790589316857,"version":"4.1.0"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. The liver is its most common site of metastasis, and in some patients, distant metastases may become clinically apparent years after treatment of the primary tumor. Metastatic UM generally shows limited responsiveness to immune checkpoint blockade. Although genetic alterations in GNAQ, GNA11, BAP1, SF3B1, and EIF1AX are important for the molecular classification and prognostic stratification of UM, these factors do not fully explain late metastatic recurrence, persistence of low-proliferative tumor cell states, immune escape, or adaptation to the hepatic metastatic microenvironment. Lactate is not only a major product of glycolysis but also an immunometabolic regulator. Through monocarboxylate transporter-mediated transport, HCAR1\/GPR81 signaling, extracellular vesicle-associated transfer, and lysine lactylation, lactate influences tumor cell states, tumor\u2013immune metabolic communication, chromatin regulation, and post-transcriptional control. In UM cell studies, exogenous lactate induces a quiescence-like phenotype characterized by reduced proliferation and migration, increased oxidative metabolism, changes in chromatin organization, and elevated H3K18la levels. Tumor-derived lactate increases the stability of PD-L1 and HLA-E proteins through GPR81-related signaling, enhancing the resistance of UM cells to T cell- and NK cell-mediated killing. Under hypoxic conditions, extracellular vesicle-associated lactate participates in metabolic communication between tumor cells and immune cells, alters macrophage states, and impairs CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell effector function. Lactylation further links lactate metabolism with chromatin regulation and RNA modification-related post-transcriptional control. Studies in related ocular melanoma models indicate that H3K18la regulates YTHDF2 and ALKBH3 and thereby affects m\n                    <jats:sup>6<\/jats:sup>\n                    A- and m\u00b9A-associated RNA regulation. This review summarizes current studies on lactate production, transport, receptor signaling, extracellular vesicle-associated lactate transfer, and lactylation in UM and related ocular melanoma models, and discusses their roles in low-proliferative adaptation, tumor\u2013immune metabolic communication, hepatic metastatic microenvironment adaptation, and therapeutic resistance.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1965851","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T08:58:57Z","timestamp":1790585937000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Lactate metabolism and lactylation in uveal melanoma: from metabolic adaptation to immune regulation"],"prefix":"10.3389","volume":"17","author":[{"given":"Yingluan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, The Second Affiliated Hospital of Harbin Medical 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