{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T13:04:17Z","timestamp":1784725457679,"version":"3.55.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Although nucleophosmin (NPM1) is a well-characterized oncogene in acute myeloid leukemia, much less is known about its role in solid tumor immunity. Here, we examined the function of NPM1 in regulating anti-tumor immunity within the tumor microenvironment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The proportion and functional changes of macrophages and T cells were detected by flow cytometry, the downstream regulatory genes of\n                      <jats:italic>NPM1<\/jats:italic>\n                      were detected by RNA-seq, the binding ability of NPM1 and STAT3 was analyzed by Chip and luciferase assay.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      NPM1 inhibition or genetic deficiency promoted tumor growth in MC38 colon cancer and LLC lung cancer mice models.\n                      <jats:italic>\n                        Npm1\n                        <jats:sup>+\/-<\/jats:sup>\n                      <\/jats:italic>\n                      mice exhibited enhanced infiltration and polarization of immunosuppressive M2-like tumor-associated macrophages (TAMs) and impaired CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell function. Mechanistically, NPM1 bound to p-TAT3\/STAT3 and promoted transcription of CCRL2, a key regulator of macrophage polarization. Overexpression of\n                      <jats:italic>Npm1<\/jats:italic>\n                      in mice suppressed tumor growth, reduced M2 TAMs polarization, and enhanced CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell-mediated anti-tumor immunity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings revealed that NPM1 protects against tumor progression by regulating TAMs polarization and T cell function via the STAT3-CCRL2 axis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1748791","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T12:08:26Z","timestamp":1784722106000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Macrophage NPM1 drives anti-tumor immunity via the STAT3-CCRL2 axis"],"prefix":"10.3389","volume":"17","author":[{"given":"Lei","family":"Hong","sequence":"first","affiliation":[{"name":"School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China","place":["Hefei, China"]},{"name":"Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Yang","sequence":"additional","affiliation":[{"name":"Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science","place":["Suzhou, China"]},{"name":"Department of Chemistry, College of Sciences, Shanghai University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuwen","family":"Han","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China","place":["Hefei, China"]},{"name":"Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Ouyang","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China","place":["Hefei, China"]},{"name":"Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minxuan","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China","place":["Hefei, China"]},{"name":"Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science","place":["Suzhou, 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