{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T18:28:18Z","timestamp":1789237698176,"version":"build-2803163510"},"reference-count":57,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82372997"],"award-info":[{"award-number":["82372997"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82573128"],"award-info":[{"award-number":["82573128"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Throughout oral squamous cell carcinoma (OSCC) progression, tumor\u2010associated macrophages (TAMs) lose their antigen\u2010presenting capacity and anti\u2010tumor function. The mechanisms that cause this dysfunction are not fully understood. CD74 is essential for antigen\u2010presenting process, while little direct evidence describes its role in TAMs' immune function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated single\u2010cell transcriptomic analysis, clinical cohort validation and CD74 conditional knockout mouse model to investigate the role of CD74 in TAMs during OSCC progression. Metabolomic analysis and mechanistic studies were performed to dissect how lactate\u2010mediated metabolic reprogramming regulates CD74 expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We demonstrate that lactate accumulation in TME induces metabolic reprogramming of TAMs, which drives the acetylation of C\/EBP\u03b1, and consequently suppresses CD74 expression. This downregulation of CD74 impairs the antigen\u2010presenting capacity of TAMs, suppresses T cell activation, and ultimately promotes OSCC progression and recurrence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings reveal the critical role of the lactate\u2010C\/EBP\u03b1\u2010CD74 axis in shaping TAMs function, and provide potential therapeutic target for OSCC immunotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            CD74\n                            <jats:sup>hi<\/jats:sup>\n                            TAMs decrease during OSCCprogression and are associated with patient prognosis.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Loss of CD74 impairs antigen presentation andsuppresses T cell activation.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Tumor\u2010derived lactateinhibits CD74 transcription via C\/EBP\u03b1 acetylation.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70639","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T09:37:11Z","timestamp":1773135431000},"source":"Crossref","is-referenced-by-count":3,"title":["Lactate\u2010induced metabolic reprogramming of TAMs impairs antigen presentation capacity via C\/EBP\u03b1\u2013CD74 axis in oral squamous cell carcinoma"],"prefix":"10.1002","volume":"16","author":[{"given":"Mengyao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Basic Science of Stomatology The Affiliated Stomatological Hospital of Nanjing Medical University  Nanjing China"},{"name":"State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Basic Science of Stomatology The Affiliated Stomatological Hospital of Nanjing Medical University  Nanjing China"},{"name":"State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zizhen","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Basic Science of Stomatology The Affiliated Stomatological Hospital of Nanjing Medical University  Nanjing China"},{"name":"State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanrui","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Basic Science of Stomatology The Affiliated Stomatological Hospital of Nanjing Medical University  Nanjing China"},{"name":"State Key Laboratory Cultivation Base of Research, Prevention and Treatment 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