{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:17:29Z","timestamp":1792700249626,"version":"4.5.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"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                    Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with tumor heterogeneity and chemoresistance posing significant therapeutic challenges. In this study, we investigated the role of tumor-macrophage interactions in CRC progression. Using single-cell RNA sequencing (scRNA-seq) analysis from public database, patient-derived organoid models, and\n                    <jats:italic>in vivo<\/jats:italic>\n                    mouse models, we demonstrated that IGLC3\n                    <jats:sup>-<\/jats:sup>\n                    tumor cells secreted TGF-\u03b2 to polarize M0 macrophages into an SPP1\n                    <jats:sup>+<\/jats:sup>\n                    , M2-like phenotype. These SPP1\n                    <jats:sup>+<\/jats:sup>\n                    macrophages enhanced tumor cell proliferation, stemness, and migration via CD44\u2013Wnt\u2013BTF3 signaling pathway. Inhibition of CD44 or Wnt signaling with HH1 or a Wnt inhibitor effectively reversed macrophage-mediated chemoresistance and suppressed tumor growth and metastasis. Notably, HH1 exhibited superior safety compared to the Wnt agonist, making it a promising candidate for combination therapy. These findings provide novel insights into tumor heterogeneity and macrophage-mediated chemoresistance, highlighting actionable targets within the tumor microenvironment to improve CRC treatment outcomes.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1731216","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T05:41:27Z","timestamp":1775022087000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["IGLC3- tumor cells drive chemoresistance in colorectal cancer by polarizing SPP1+ macrophages via the CD44-Wnt-BTF3 axis"],"prefix":"10.3389","volume":"17","author":[{"given":"Feihu","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Colorectal Surgery, Changhai Hospital of Naval Medical University, Naval Medical University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunjie","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Changhai Hospital of Naval Medical University, Naval Medical University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hantao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Changhai Hospital of Naval Medical University, Naval Medical University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingchen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Changhai Hospital of Naval Medical University, Naval Medical University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiwen","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Changhai Hospital of Naval Medical University, Naval Medical University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Changhai Hospital of Naval Medical University, Naval Medical University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Changhai Hospital of Naval Medical University, Naval Medical University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Changhai Hospital of Naval Medical University, Naval Medical University","place":["Shanghai, 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