{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:03:54Z","timestamp":1784783034428,"version":"3.55.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K06127"],"award-info":[{"award-number":["23K06127"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>\n                    Epidermal growth factor-like domain 7 (EGFL7) was discovered as an extracellular matrix protein with an EGF-like domain and angiogenic and vasculogenic functions. It has also been shown to play a role in immunological evasion of tumor cells through attenuation of extravasation of immune cells by reducing the expression of cell adhesion molecules on vascular endothelial cells. Furthermore, microRNA-126 (miR-126), which is encoded within the intron of\n                    <jats:italic>Egfl7<\/jats:italic>\n                    , has been reported to be a vasculogenic factor. However, its immune-related functions in tumors remain unclear. Here, we examined the roles of tumor-derived EGFL7 and miR-126 in\n                    <jats:italic>in vivo<\/jats:italic>\n                    tumor progression using\n                    <jats:italic>Egfl7\/Mir-126<\/jats:italic>\n                    knockout and rescue tumor cell lines. Tumor growth was significantly suppressed in\n                    <jats:italic>Egfl7\/Mir-126<\/jats:italic>\n                    -deficient cells and was restored by re-expression of miR-126, but not EGFL7. These differences in\n                    <jats:italic>in vivo<\/jats:italic>\n                    tumor growth were not observed in immunodeficient mice, suggesting the involvement of the adaptive immune system. CD4\n                    <jats:sup>+<\/jats:sup>\n                    or CD25\n                    <jats:sup>+<\/jats:sup>\n                    cell depletion suppressed the growth of miR-126-expressing tumors, whereas CD8\n                    <jats:sup>+<\/jats:sup>\n                    cell depletion enhanced the growth of miR-126-deficient tumors. Histological analysis revealed an increased Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    \/CD8\n                    <jats:sup>+<\/jats:sup>\n                    cell ratio in miR-126-expressing tumors during the early phase of tumor establishment. Bilateral tumor models further demonstrated that miR-126-expressing tumors promoted the growth of contralateral miR-126-deficient tumors, and a similar effect was observed using apoptotic miR-126-expressing tumor cells\n                    <jats:italic>In vitro<\/jats:italic>\n                    analyses using extracellular vesicles derived from dying tumor cells showed the transfer of miR-126 to CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and a higher proportion of Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    cells. Together, these findings suggest that tumor-derived miR-126 promotes tumor progression through non-local immune modulation, potentially involving maintenance of Treg-associated populations.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2026.1867336","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T04:28:10Z","timestamp":1784780890000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumor-derived miR-126 promotes tumor progression through immune modulation beyond the local tumor environment"],"prefix":"10.3389","volume":"16","author":[{"given":"Takashi","family":"Akazawa","sequence":"first","affiliation":[{"name":"Department of Cancer Drug Discovery and Development, Research Center, Osaka International Cancer Institute","place":["Osaka, Japan"]},{"name":"Department of Cancer Immunotherapy, Frontier Exploratory Research Domain, Next-Generation Precision Cancer Research Center, Osaka International Cancer Institute","place":["Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Mizote","sequence":"additional","affiliation":[{"name":"Department of Cancer Drug Discovery and Development, Research Center, Osaka International Cancer Institute","place":["Osaka, Japan"]},{"name":"Department of Cancer Immunotherapy, Frontier Exploratory Research Domain, Next-Generation Precision Cancer Research Center, Osaka International Cancer Institute","place":["Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoya","family":"Ekawa","sequence":"additional","affiliation":[{"name":"Department of Cancer Drug Discovery and Development, Research Center, Osaka International Cancer Institute","place":["Osaka, Japan"]},{"name":"Department of Cancer Immunotherapy, Frontier Exploratory Research Domain, Next-Generation Precision Cancer Research Center, Osaka International Cancer Institute","place":["Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satomi","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Cancer Drug Discovery and Development, Research Center, Osaka International Cancer Institute","place":["Osaka, Japan"]},{"name":"Department of Cancer Immunotherapy, Frontier Exploratory Research Domain, Next-Generation Precision Cancer Research Center, Osaka International Cancer Institute","place":["Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yachiyo","family":"Kumamoto","sequence":"additional","affiliation":[{"name":"Department of Cancer Drug Discovery and Development, Research Center, Osaka International Cancer Institute","place":["Osaka, Japan"]},{"name":"Department of Cancer Immunotherapy, Frontier Exploratory Research Domain, Next-Generation Precision Cancer Research Center, Osaka International Cancer Institute","place":["Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichiro","family":"Harada","sequence":"additional","affiliation":[{"name":"Department of Glyco-Oncology and Medical Biochemistry, Research Center, Osaka International Cancer Institute","place":["Osaka, Japan"]},{"name":"Institute for Glyco-core Research (iGCORE), Nagoya University","place":["Nagoya, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisataka","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Nitto Joint Research Department for Nucleic Acid Medicine, Research Center, Osaka International Cancer Institute","place":["Osaka, Japan"]},{"name":"Department of Surgery, Rinku General Medical Center","place":["Izumisano, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunichi","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Cancer Drug Discovery and Development, Research Center, Osaka International Cancer Institute","place":["Osaka, Japan"]},{"name":"Department of Cancer Immunotherapy, Frontier Exploratory Research Domain, Next-Generation Precision Cancer Research Center, Osaka International Cancer Institute","place":["Osaka, Japan"]},{"name":"Department of Advanced Pathobiology, Graduate School of Veterinary Science, Osaka Metropolitan University","place":["Izumisano, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shingo","family":"Hatoya","sequence":"additional","affiliation":[{"name":"Department of Advanced Pathobiology, Graduate School of Veterinary Science, Osaka Metropolitan University","place":["Izumisano, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norimitsu","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Wakayama Medical University","place":["Wakayama, 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