{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T21:41:54Z","timestamp":1793742114660,"version":"4.6.1"},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","funder":[{"DOI":"10.13039\/100007082","name":"Pharmavite","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007082","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031022","name":"Center for Cancer Research","doi-asserted-by":"publisher","award":["NIH\/NCI P50CA127003"],"award-info":[{"award-number":["NIH\/NCI P50CA127003"]}],"id":[{"id":"10.13039\/100031022","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031022","name":"Center for Cancer Research","doi-asserted-by":"publisher","award":["NIH\/NCI R01205406"],"award-info":[{"award-number":["NIH\/NCI R01205406"]}],"id":[{"id":"10.13039\/100031022","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Although vitamin D (VitD) exhibits antitumor activity in colorectal cancer preclinically, its effects in the human tumor microenvironment (TME) remain unclear. We conducted a randomized, placebo-controlled trial of preoperative high-dose VitD supplementation in patients with stage I to III colon cancer to assess its impact on the TME. Forty-two patients received either VitD3 (50,000 IU\/day for 7 days, then 10,000 IU\/day) or placebo before surgery. Spatial immune profiling and assessment of VitD receptor (VDR) and CYP27B1 expression were performed on paired tumor samples from 24 patients. VitD significantly increased plasma 25-hydroxyvitamin D levels (P &amp;lt; 0.001), increased CD3+CD8+ memory T cells (P = 0.03), reduced CD3+CD4+FoxP3+ regulatory T cells (P = 0.02), and spatially re-organized the TME, leading to greater T-cell and tumor cell proximity. Posttreatment VDR expression was heterogeneous and decreased overall (P = 0.02). Spatial transcriptomic profiling of posttreatment resections reflected predominantly repressive VDR activity. These findings support an immunomodulatory role for VitD, warranting further mechanistic investigation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>Colorectal cancer remains a leading cause of cancer-related death with limited long-term survival. We evaluated the effects of short-term, preoperative high-dose VitD supplementation on the colon cancer microenvironment in a randomized, placebo-controlled trial. Our findings support VitD as an immune modulator and may inform future treatment strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-25-1574","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T12:27:19Z","timestamp":1783513639000},"page":"OF1-OF18","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Impact of Vitamin D on the Colon Cancer Immune Microenvironment: Results of a Randomized Clinical Trial of Preoperative Vitamin D Supplementation in Patients with Stage I\u2013III Colon Cancer"],"prefix":"10.1158","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1046-4899","authenticated-orcid":false,"given":"Andressa","family":"Dias Costa","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02jzgtq86","id-type":"ROR","asserted-by":"publisher"}],"name":"Dana-Farber Cancer Institute 1 Department of Medical Oncology, , Harvard Medical School, 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