{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:46:47Z","timestamp":1787496407929,"version":"build-2736575974"},"reference-count":45,"publisher":"BMJ","issue":"12","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"unspecified","delay-in-days":17,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["AIRC IG 29244"],"award-info":[{"award-number":["AIRC IG 29244"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["AIRC MFAG 23192"],"award-info":[{"award-number":["AIRC MFAG 23192"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,11,18]]},"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Colorectal cancer (CRC) progression is shaped by the tumor microenvironment, particularly tumor-associated macrophages (TAMs), which often adopt immunosuppressive functions. CD300e, a myeloid receptor involved in immune regulation, has an uncharacterized role in CRC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Functional studies were conducted in azoxymethane\/dextran sodium sulfate and MC38 murine CRC models using CD300e systemic and myeloid-specific CD300e knockout mice, and adoptive transfer experiments assessed macrophage-intrinsic effects. Human studies included analysis of CD300e expression in matched tumor and normal tissue from patients with CRC and in vitro co-culture of patient-derived colon tumor organoids with monocytes to study CD300e induction and TAM polarization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In vivo, CD300e deficiency led to reduced tumor burden, enhanced major histocompatibility complex expression on TAMs, and improved T-cell responses. CD300e-deficient macrophages exhibited increased phagocytic activity, antigen presentation, and support for T-cell proliferation and cytotoxicity. Adoptive transfer confirmed that macrophage-intrinsic CD300e expression is sufficient to suppress T-cell function and promote tumor growth. In patients with CRC, CD300e is selectively upregulated in tumor-infiltrating monocytes and macrophages, driving a suppressive phenotype marked by impaired antigen presentation. Tumor-derived signals in vitro induce CD300e expression and promote a protumorigenic macrophage profile.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings identify CD300e as a critical regulator of macrophage-mediated immune suppression in CRC and a potential target for reprogramming TAMs to enhance immunotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-013249","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T01:40:29Z","timestamp":1766022029000},"page":"e013249","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["CD300e is a driver of the immunosuppressive tumor microenvironment and colorectal cancer progression via macrophage 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