{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:23:24Z","timestamp":1787729004080,"version":"build-2784847793"},"reference-count":34,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82470691"],"award-info":[{"award-number":["82470691"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Colorectal cancer (CRC) is a leading cause of cancer\u2010related death and is associated with high recurrence rates. Solute carrier family 7 member 5 (SLC7A5), a core transporter that facilitates the transmembrane movement of tryptophan, plays a role in various cancers. However, whether and how SLC7A5 promotes colorectal liver metastasis (CRLM) through tryptophan metabolism reprogramming and immune remodelling remain unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated public datasets and clinical specimens to analyse SLC7A5 expression and prognosis, and validated its role in proliferation and metastasis using in vitro assays and in vivo models. Targeted metabolomics and isotope tracing identified kynurenine (Kyn) and xanthurenic acid (XANA) as downstream metabolites of SLC7A5. Single\u2010cell RNA sequencing (scRNA\u2010seq) and conditioned medium experiments were used to assess the impact of SLC7A5 on the tumour immune microenvironment (TIME).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      SLC7A5 expression increases sequentially in normal tissue, primary tumours and liver metastases, and higher SLC7A5 levels are associated with worse prognosis. SLC7A5 facilitates CRC cell growth, metastasis and epithelial\u2012mesenchymal transition (EMT) by promoting the production of Kyn and XANA and subsequent activation of the aryl hydrocarbon receptor (AhR). scRNA\u2010seq analysis and conditioned medium experiments demonstrated that SLC7A5 knockdown reprograms the TIME by driving macrophages towards an antigen\u2010presenting phenotype, alleviating CD8\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell exhaustion, polarising CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells towards Th1\/Th17 subsets and triggering antigen\u2010driven immunoglobulin G (IgG)\u2010secreting B\u2010cell clonal expansion, effects that were reversed by exogenous Kyn\/XANA supplementation. Moreover, combination therapy with the SLC7A5 inhibitor JPH203 and anti\u2010programmed cell death protein 1 (PD\u20101) antibody produced synergistic tumour growth inhibition and heightened antitumour immune responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Collectively, our findings reveal that SLC7A5 drives CRLM through tryptophan\/Kyn\/XANA\u2013AhR signalling and concomitant remodelling of the TIME, positioning SLC7A5 as a promising target for combination therapy with anti\u2010PD\u20101 in CRLM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70766","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T06:35:53Z","timestamp":1786084553000},"source":"Crossref","is-referenced-by-count":0,"title":["SLC7A5 promotes colorectal cancer liver metastasis by reprogramming tryptophan metabolism through the Kyn\/XANA\u2012AhR axis and reshaping the immune microenvironment"],"prefix":"10.1002","volume":"16","author":[{"given":"Yaohao","family":"Luo","sequence":"first","affiliation":[{"name":"Department of General Surgery Shanghai General Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of General Surgery Shanghai General Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanbao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of General Surgery Shanghai General Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinshuai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Surgery Shanghai General Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeping","family":"He","sequence":"additional","affiliation":[{"name":"Department of General Surgery Shanghai General Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangbin","family":"Song","sequence":"additional","affiliation":[{"name":"Department of General Surgery Shanghai General Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of General Surgery Shanghai General Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department 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