{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:47:58Z","timestamp":1792122478838,"version":"4.4.0"},"reference-count":41,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Yantai Science and Technology Innovation Development Program","award":["2023JCYJ070"],"award-info":[{"award-number":["2023JCYJ070"]}]},{"name":"Shandong Provincial College Youth Innovation and Talent Cultivation Plan, National Natural Science Foundation of China","award":["82470587"],"award-info":[{"award-number":["82470587"]}]},{"name":"Initial Project from Binzhou Medical University","award":["50012304420"],"award-info":[{"award-number":["50012304420"]}]},{"name":"The Yantai Science and Technology Innovation Development Program","award":["No. 2023JCYJ070"],"award-info":[{"award-number":["No. 2023JCYJ070"]}]},{"name":"Shandong Provincial College Youth\u00a0Innovation and Talent Cultivation Plan"},{"name":"Initial Project from Binzhou Medical University","award":["No. 50012304420"],"award-info":[{"award-number":["No. 50012304420"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["No. 82470587"],"award-info":[{"award-number":["No. 82470587"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    The contribution of putrescine (PUT) metabolism to impaired tumor immunosurveillance in colorectal cancer (CRC) requires a thorough examination of its biosynthesis, catabolism, and transport during tumor development. This study found, unexpectedly, that a better prognosis was associated with higher expression of the PUT biosynthesis genes\n                    <jats:italic>ODC1<\/jats:italic>\n                    and\n                    <jats:italic>AGMAT<\/jats:italic>\n                    , while elevated expression of biosynthesis inhibitors and transport genes predicted worse outcomes. Two independent cohorts were deconvoluted by integrating data from 517,191 cells across 221 samples from 131 subjects. Higher percentages of epithelial subpopulations with low PUT transport scores were linked to improved prognosis. In contrast, greater proportions of T\/natural killer\/ILC cells with low biosynthesis but relatively higher transport scores were associated with poorer outcomes. PUT supplementation in HCT-116 and RKO cells promoted the tumor cell proliferation, but had no effect on cell migration or the expression of N-cadherin and E-cadherin. CXCR6\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, which were more prevalent in tumor tissue, exhibited significantly higher cytotoxicity compared to CXCR6\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, as assessed using updated gene sets for T cell functional evaluation . However, CXCR6\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells also displayed elevated markers of exhaustion. Notably, higher CXCR6 expression and increased infiltration of CXCR6\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells correlated with improved prognosis in both mismatch repair-proficient and mismatch repair-deficient CRC. To estimate the local accumulation of PUT around CXCR6\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, a novel \u201cPi value\u201d was defined. A negative correlation was found between Pi values and both the cytotoxic activity and pro-inflammatory potential of these cells. Further investigation using a CRC tumor antigen-based\n                    <jats:italic>in vitro<\/jats:italic>\n                    system for the efficient induction of CXCR6\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells revealed that extracellular PUT inhibits their cytotoxic function. Additionally, in a Dextran Sulfate Sodium (DSS)-induced colitis model combined with single-cell RNA sequencing, PUT supplementation resulted in the elimination of CXCR6\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in the colon. These findings provide new insights into how polyamine metabolism, particularly involving extracellular PUT, impairs the anti-tumor activity of CXCR6\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, potentially contribut ing to CRC progression.\n                  <\/jats:p>","DOI":"10.7717\/peerj.20663","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T08:13:15Z","timestamp":1770883995000},"page":"e20663","source":"Crossref","is-referenced-by-count":1,"title":["Multiomics analysis of polyamine metabolism in colorectal cancer, highlighting the key role of extracellular putrescine in impairing CXCR6\n                    <sup>+<\/sup>\n                    CD8\n                    <sup>+<\/sup>\n                    T cell anti-tumor activity"],"prefix":"10.7717","volume":"14","author":[{"given":"Ziru","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Institute of Digestive Disease, Binzhou Medical University Hospital, Binzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Yantai Affiliated Hospital of Binzhou Medical University, Department of Clinical Laboratory, Yantai, China"},{"name":"Department of Laboratory Medicine, The First Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"pei jia","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Institute of Digestive Disease, Binzhou Medical University Hospital, Binzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifeng","family":"Lian","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Institute of Digestive Disease, Binzhou Medical University Hospital, Binzhou, China"},{"name":"Department of Gastroenterology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Institute of Digestive Disease, Binzhou Medical University Hospital, Binzhou, China"},{"name":"Department of Immunology, Binzhou Medical University, Binzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4443","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"key":"10.7717\/peerj.20663\/ref-1","doi-asserted-by":"publisher","first-page":"2012","DOI":"10.1158\/1535-7163.Mct-19-1116","article-title":"Polyamine 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