{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:09:14Z","timestamp":1788930554629,"version":"build-2803163510"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"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>Immune regulatory networks contribute to colorectal cancer (CRC) progression, but most clinical studies focus on tissue immune-cell abundance or static inflammatory mediators. We investigated cytokine-response patterns in cultures derived from peripheral-blood CD14+ cells and local immune-cell composition in tumor-adjacent and resection-margin mucosa.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This single-center prospective observational study included 106 patients with colorectal adenocarcinoma and 20 comparison subjects with non-malignant surgical conditions. Peripheral-blood CD14+ cells were isolated, differentiated with M-CSF, and subjected to sequential LPS stimulation. IL-1\u03b2, IL-6, IL-8, and MCP-1 concentrations were measured, and cytokine-response indices were calculated. In CRC patients, CD4+, CD8+, CD20+, CD56+, and CD68+ cell densities were quantified immunohistochemically in paired mucosal compartments. Analyses addressed CRC-associated differences, local immune-cell organization, systemic\u2013local associations, and an exploratory comparison between patients without distant metastases (n = 97) and patients with distant metastases (n = 9).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CRC was associated with selective remodeling of IL-1\u03b2 and IL-6 response indices. Compared with the comparison group, CRC patients showed higher IL-1\u03b2 post-washout persistence, lower shutdown efficiency and re-induction capacity, and a higher re-stimulation index. IL-6 responses were characterized by lower basal activity but higher basal drift, primary LPS response, and post-washout persistence. The exploratory comparison according to distant metastasis status identified additional differences in selected IL-1\u03b2 and IL-6 indices, however, these findings are limited by the small number of patients with distant metastases. Locally, CD20+ cells were enriched in tumor-adjacent mucosa, whereas CD68+ cells were enriched in resection-margin mucosa. Matched immune-cell densities were positively correlated across compartments. The strongest systemic-local association was an inverse correlation between MCP-1 primary LPS response and CD68+ cell density in tumor-adjacent mucosa.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CRC is associated with altered cytokine responsiveness in M-CSF-differentiated cultures derived from blood CD14+ cells and with compartment-specific mucosal immune-cell organization. The observed systemic\u2013local associations suggest partial coupling between these experimental and tissue-level immune features. Exploratory metastasis-associated patterns were identified but require validation in larger, adequately powered cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1918710","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:42:14Z","timestamp":1788928934000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Systemic\u2013local immune remodeling in colorectal cancer: CD14+ cell-derived cytokine responsiveness, mucosal immune-cell organization, and exploratory metastasis-associated patterns"],"prefix":"10.3389","volume":"17","author":[{"given":"Nikolay K.","family":"Shakhpazyan","sequence":"first","affiliation":[{"name":"Petrovsky National Research Centre of Surgery","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liudmila M.","family":"Mikhaleva","sequence":"additional","affiliation":[{"name":"Petrovsky National 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