{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:50:46Z","timestamp":1791895846659,"version":"4.3.4"},"reference-count":61,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81903864"],"award-info":[{"award-number":["81903864"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Integr Cancer Ther"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Tryptophan metabolism plays a pivotal role in promoting tumor progression by modulating immune escape in breast cancer (BC). Shugan-Liangxue prescription (SLP), a traditional Chinese medicine, has shown beneficial effects in enhancing antitumor immunity for BC treatment. This study aims to investigate the effect of SLP on tryptophan metabolism in BC and to explore the underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The immunopharmacological BC model in rats was established by chemical carcinogen induction and complete freund\u2019s adjuvant perturbations and treated with SLP. Tamoxifen and other metabolism-associated drugs were used as controls. The therapeutic efficacy of SLP was evaluated by tumor volume, weight, and oncocyte proliferation. Serum cytokines and subsets of immune cells in the spleen were measured to evaluate the anti-tumor immunity. Metabolite levels and expressions of signal molecules of tryptophan metabolic pathway were measured to explore the mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our findings demonstrated that SLP treatment significantly inhibited tumor growth and tumor cell proliferation, and enhanced antitumor immunity by promoting Th1 polarization, increasing cytotoxic immune cells (CD8+ T cells, NKG2D+ NK cells), and reducing inhibitory immune cells (Foxp3+ Tregs, NKG2A+ NK cells, M2 macrophages) in the spleen. Additionally, SLP regulated glucose and lipid metabolism, as evidenced by reduced serum glucose and non-esterified fatty acid levels. SLP suppressed tryptophan catabolism by down-regulating expression of IDO1 and AhR and reducing kynurenine levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In summary, correlative analyses suggest SLP may mitigate breast cancer immune escape partially via the Trp metabolic pathway to boost anti-tumor immune surveillance, and its immunomodulatory activity is potentially linked to glucose and lipid reprogramming. While our findings support the involvement of the Trp-Kyn-AhR axis, causal verification via pathway rescue and inhibition assays is still needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15347354261494127","type":"journal-article","created":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T10:41:21Z","timestamp":1791715281000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Shugan-Liangxue Prescription Inhibits Immune Escape Against Breast Cancer by Regulating Tryptophan Metabolism"],"prefix":"10.1177","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9426-1864","authenticated-orcid":false,"given":"Youzhan","family":"Yang","sequence":"first","affiliation":[{"name":"Beijing University of Chinese Medicine"},{"name":"China-Japan Friendship Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runjia","family":"Shi","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine"},{"name":"China-Japan Friendship Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoya","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulin","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayong","family":"Cai","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4363-5465","authenticated-orcid":false,"given":"Zhiqiang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine"},{"name":"China-Japan Friendship Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,10,11]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_3_3_3_2","volume-title":"Global Cancer Observatory: Cancer Today","author":"Ferlay J","year":"2024","unstructured":"Ferlay J, Ervik M, Lam F, et al. Global Cancer Observatory: Cancer Today, 2024. Lyon, France: International Agency for Research on Cancer; 2024. (July 11)."},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/35021093"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.5114\/pjp.2014.42672"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/rpd\/ncu243"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2019.12.018"},{"key":"e_1_3_3_8_2","first-page":"2024","volume-title":"NCCN Clinical Practice Guidelines in Breast Cancer (Version 2024.3)","author":"NCCN","year":"2024","unstructured":"NCCN. NCCN Clinical Practice Guidelines in Breast Cancer (Version 2024.3); 2024:2024. July 11."},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells14171353"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-026-02582-0"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1023\/a:1010602822483"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-012-9482-7"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2023.188861"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.06.003"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.34133\/bmr.0048"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.9.1363"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200636704"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpt.2023.11.001"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S373780"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2023.06.010"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20201606"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-020-0375-3"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/189204a0"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2015.11.004"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0254-6272(18)30981-6"},{"issue":"25","key":"e_1_3_3_27_2","first-page":"2670","article-title":"Study on extraction technology of compound Chaihu granule by multi-index optimization and its preparation","volume":"11","author":"Feng L","year":"2014","unstructured":"Feng L, Tian M, Zhang D, et al. Study on extraction technology of compound Chaihu granule by multi-index optimization and its preparation. Lishizhen Medicine and Materia Medica Research. 2014;11(25):2670-2672NA.","journal-title":"Lishizhen Medicine and Materia Medica Research"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0027-5107(96)00162-5"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.155"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2017.03.007"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature17412"},{"key":"e_1_3_3_32_2","first-page":"409","article-title":"Preliminary Evidence for Curative Effect of BCG on Chemically Induced Carcinoma of Mammary Gland of Female Albino Rat","volume":"44","author":"Sultana TTM","year":"2012","unstructured":"Sultana TTM. Preliminary Evidence for Curative Effect of BCG on Chemically Induced Carcinoma of Mammary Gland of Female Albino Rat. Pak J Zool. 2012;44:409-414.","journal-title":"Pak J Zool"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1080\/14789450.2020.1845654"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2018.12.023"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2013.128"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2013.06.004"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1155\/2007\/24147"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12672-024-01309-1"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.09.004"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.09.001"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2021.03.019"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.35"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-2285"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.583084"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.887503"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.747780"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2018.00423"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-2882"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2017.11.007"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12282-023-01522-w"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6467"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-017-0285-7"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-020-0273-y"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-017-7215-0_8"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-005-0010-3"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13490"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2077"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2023.2244330"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2023.101700"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2024.159531"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.04.002"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2014.11.004"}],"container-title":["Integrative Cancer Therapies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/15347354261494127","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/15347354261494127","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/15347354261494127","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:18:40Z","timestamp":1791893920000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/15347354261494127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":61,"alternative-id":["10.1177\/15347354261494127"],"URL":"https:\/\/doi.org\/10.1177\/15347354261494127","relation":{},"ISSN":["1534-7354","1552-695X"],"issn-type":[{"value":"1534-7354","type":"print"},{"value":"1552-695X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"article-number":"15347354261494127"}}