{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T20:07:23Z","timestamp":1789848443023,"version":"4.0.1"},"reference-count":34,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Gemcitabine (GEM), a first\u2010line chemotherapeutic agent, may fail to prevent recurrence in some settings. Traditional Chinese medicine emphasizes Yin\u2013Yang balance and \u201cfuzheng\u201d approaches and may offer complementary strategies.\n                    <jats:italic>Ganoderma lucidum<\/jats:italic>\n                    polysaccharides (GLP) exhibit immune\u2010enhancing activity, but evidence for direct anti\u2010tumor efficacy, either alone or in combination with low\u2010dose GEM, remains limited. Using a murine 4T1 breast cancer model, we integrated flow cytometry, 16S rRNA gene sequencing, and gas chromatography\u2013mass spectrometry to evaluate the anti\u2010tumor activity of GLP combined with low\u2010dose GEM. GLP alone enhanced immune parameters but did not significantly suppress tumor growth, whereas low\u2010dose GEM reduced tumor volume and activated anti\u2010tumor immunity. Notably, the GLP plus GEM combination produced greater tumor inhibition than either treatment alone and was associated with increased IFN\u2010\u03b3 and TNF\u2010\u03b1 levels, enhanced CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell infiltration, and enrichment of\n                    <jats:italic>Ligilactobacillus, Duncaniella,<\/jats:italic>\n                    and\n                    <jats:italic>Faecalibaculum<\/jats:italic>\n                    in the gut microbiota, and elevated serum levels of short\u2010chain fatty acids and tryptophan. Notably, the antitumor effect in the combination group was accompanied by reduced tumoral IDO expression and elevated serum tryptophan, which were statistically correlated; however, as kynurenine levels were not quantified in this study, we cannot attribute this correlation to altered IDO enzymatic activity or establish a direct functional link along the IDO\u2013tryptophan metabolic pathway. Thus, the combination of GLP and low\u2010dose GEM exerts a synergistic anti\u2010tumor effect.\n                  <\/jats:p>","DOI":"10.1002\/mc.70178","type":"journal-article","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T19:45:51Z","timestamp":1789847151000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ganoderma Lucidum Polysaccharides Potentiate Low\u2010Dose Gemcitabine Against 4T1 Breast Tumors, Associated With Immune Activation and Gut Microbiota Remodeling"],"prefix":"10.1002","author":[{"given":"Wenli","family":"Zhang","sequence":"first","affiliation":[{"name":"Translational Medicine Center of Shaanxi Provincial People's Hospital Xi'an China"},{"name":"Shaanxi Engineering Research Center of Cell Immunological Shaanxi Provincial People's Hospital Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo","family":"Chen","sequence":"additional","affiliation":[{"name":"Translational Medicine Center of Shaanxi Provincial People's Hospital Xi'an China"},{"name":"Shaanxi Engineering Research Center of Cell Immunological Shaanxi Provincial People's Hospital Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangyu","family":"Li","sequence":"additional","affiliation":[{"name":"Translational Medicine Center of Shaanxi Provincial People's Hospital Xi'an China"},{"name":"Shaanxi Engineering Research Center of Cell Immunological Shaanxi Provincial People's Hospital Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penghua","family":"Zhao","sequence":"additional","affiliation":[{"name":"Translational Medicine Center of Shaanxi Provincial People's Hospital Xi'an China"},{"name":"Shaanxi Engineering Research Center of Cell Immunological Shaanxi Provincial People's Hospital Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Cheng","sequence":"additional","affiliation":[{"name":"The Breast Disease Surgical Center in Shaanxi Provincial People's Hospital Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5390-5020","authenticated-orcid":false,"given":"Zifan","family":"Lu","sequence":"additional","affiliation":[{"name":"Translational Medicine Center of Shaanxi Provincial People's Hospital Xi'an China"},{"name":"Shaanxi Engineering Research Center of Cell Immunological Shaanxi Provincial People's Hospital Xi'an China"},{"name":"Department of Biopharmaceutics Fourth Military Medical University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangjun","family":"Song","sequence":"additional","affiliation":[{"name":"The Breast Disease Surgical Center in Shaanxi Provincial People's Hospital Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,19]]},"reference":[{"issue":"2","key":"e_1_2_11_2_1","first-page":"69","article-title":"Global Cancer Statistics","volume":"61","author":"Jemal A.","year":"2011","journal-title":"CA: A Cancer Journal for Clinicians"},{"issue":"1","key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1007\/s12609-012-0097-1","article-title":"Chemotherapy in Patients With Anthracycline\u2010 and Taxane\u2010Pretreated Metastatic Breast Cancer: An Overview","volume":"5","author":"Andreopoulou E.","year":"2013","journal-title":"Current Breast Cancer Reports"},{"issue":"24","key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"3950","DOI":"10.1200\/JCO.2007.11.9362","article-title":"Gemcitabine Plus Paclitaxel Versus Paclitaxel Monotherapy in Patients With Metastatic Breast Cancer and Prior Anthracycline Treatment","volume":"26","author":"Albain K. 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