{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:14:44Z","timestamp":1788221684793,"version":"build-2803163510"},"reference-count":38,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Tissue and Cell"],"published-print":{"date-parts":[[2026,2]]},"DOI":"10.1016\/j.tice.2025.103202","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T18:57:56Z","timestamp":1761591476000},"page":"103202","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":5,"special_numbering":"C","title":["Lactic acid inhibits ferroptosis and promotes M2 macrophage polarization in colon cancer via GPX4 regulation"],"prefix":"10.1016","volume":"98","author":[{"given":"Xiaofei","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaqiang","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"6","key":"10.1016\/j.tice.2025.103202_bib1","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20210518","article-title":"Ferroptosis in infection, inflammation, and immunity","volume":"218","author":"Chen","year":"2021","journal-title":"J. Exp. Med"},{"issue":"12","key":"10.1016\/j.tice.2025.103202_bib2","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1038\/s41419-023-06241-w","article-title":"m6A and m5C modification of GPX4 facilitates anticancer immunity via STING activation","volume":"14","author":"Chen","year":"2023","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.tice.2025.103202_bib3","doi-asserted-by":"crossref","DOI":"10.1016\/j.canlet.2024.216837","article-title":"The emerging role of lactate in tumor microenvironment and its clinical relevance","volume":"590","author":"Chen","year":"2024","journal-title":"Cancer Lett."},{"key":"10.1016\/j.tice.2025.103202_bib4","doi-asserted-by":"crossref","first-page":"3119375","DOI":"10.1155\/2022\/3119375","article-title":"Tumor microenvironment: lactic acid promotes tumor development","volume":"2022","author":"Gao","year":"2022","journal-title":"J. Immunol. Res."},{"issue":"1","key":"10.1016\/j.tice.2025.103202_bib5","doi-asserted-by":"crossref","DOI":"10.1093\/bjs\/znad316","article-title":"Risk factors for anastomotic leak and postoperative morbidity after right hemicolectomy for colon cancer: results from a prospective, multi-centre, snapshot study in China","volume":"111","author":"Gao","year":"2024","journal-title":"Br. J. Surg."},{"issue":"19","key":"10.1016\/j.tice.2025.103202_bib6","doi-asserted-by":"crossref","DOI":"10.3390\/cancers16193410","article-title":"Tumor-associated macrophages as major immunosuppressive cells in the tumor microenvironment","volume":"16","author":"Ghebremedhin","year":"2024","journal-title":"Cancers (Basel)"},{"issue":"7","key":"10.1016\/j.tice.2025.103202_bib7","doi-asserted-by":"crossref","first-page":"2368","DOI":"10.7150\/thno.83938","article-title":"Lactate-mediated Fascin protrusions promote cell adhesion and migration in cervical cancer","volume":"13","author":"Han","year":"2023","journal-title":"Theranostics"},{"issue":"5","key":"10.1016\/j.tice.2025.103202_bib8","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0154605","article-title":"Erastin disrupts mitochondrial permeability transition pore (mPTP) and induces apoptotic death of colorectal cancer cells","volume":"11","author":"Huo","year":"2016","journal-title":"PLoS One"},{"issue":"1","key":"10.1016\/j.tice.2025.103202_bib9","doi-asserted-by":"crossref","first-page":"G59","DOI":"10.1152\/ajpgi.00123.2016","article-title":"Colonic macrophage polarization in homeostasis, inflammation, and cancer","volume":"311","author":"Isidro","year":"2016","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"issue":"4","key":"10.1016\/j.tice.2025.103202_bib10","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1007\/s43440-023-00504-1","article-title":"The Warburg effect: a score for many instruments in the concert of cancer and cancer niche cells","volume":"75","author":"Jaworska","year":"2023","journal-title":"Pharm. Rep."},{"issue":"8","key":"10.1016\/j.tice.2025.103202_bib11","doi-asserted-by":"crossref","first-page":"4934","DOI":"10.1007\/s12010-023-04789-z","article-title":"Construction and evaluation of an M2 macrophage-related prognostic model for colon cancer","volume":"196","author":"Ji","year":"2024","journal-title":"Appl. Biochem. Biotechnol."},{"issue":"7","key":"10.1016\/j.tice.2025.103202_bib12","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/s41568-022-00459-0","article-title":"Targeting ferroptosis as a vulnerability in cancer","volume":"22","author":"Lei","year":"2022","journal-title":"Nat. Rev. Cancer"},{"issue":"4","key":"10.1016\/j.tice.2025.103202_bib13","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.ccell.2024.03.011","article-title":"The roles of ferroptosis in cancer: tumor suppression, tumor microenvironment, and therapeutic interventions","volume":"42","author":"Lei","year":"2024","journal-title":"Cancer Cell"},{"issue":"9","key":"10.1016\/j.tice.2025.103202_bib14","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1038\/s41590-021-00993-3","article-title":"Glutathione peroxidase 4-regulated neutrophil ferroptosis induces systemic autoimmunity","volume":"22","author":"Li","year":"2021","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.tice.2025.103202_bib15","doi-asserted-by":"crossref","first-page":"2353115","DOI":"10.1155\/2022\/2353115","article-title":"Energy-stress-mediated AMPK activation promotes GPX4-dependent ferroptosis through the JAK2\/STAT3\/P53 axis in renal cancer","volume":"2022","author":"Li","year":"2022","journal-title":"Oxid. Med. Cell Longev."},{"issue":"1","key":"10.1016\/j.tice.2025.103202_bib16","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1080\/15548627.2023.2249762","article-title":"Tumor-derived lactate promotes resistance to bevacizumab treatment by facilitating autophagy enhancer protein RUBCNL expression through histone H3 lysine 18 lactylation (H3K18la) in colorectal cancer","volume":"20","author":"Li","year":"2024","journal-title":"Autophagy"},{"key":"10.1016\/j.tice.2025.103202_bib17","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2024.117406","article-title":"Emerging role of tumor microenvironmental nutrients and metabolic molecules in ferroptosis: mechanisms and clinical implications","volume":"179","author":"Li","year":"2024","journal-title":"Biomed. Pharm."},{"issue":"13","key":"10.1016\/j.tice.2025.103202_bib18","doi-asserted-by":"crossref","first-page":"4574","DOI":"10.7150\/thno.86928","article-title":"Histone deacetylase-mediated tumor microenvironment characteristics and synergistic immunotherapy in gastric cancer","volume":"13","author":"Lin","year":"2023","journal-title":"Theranostics"},{"issue":"8","key":"10.1016\/j.tice.2025.103202_bib19","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/s41419-023-06045-y","article-title":"The diversified role of mitochondria in ferroptosis in cancer","volume":"14","author":"Liu","year":"2023","journal-title":"Cell Death Dis."},{"issue":"8","key":"10.1016\/j.tice.2025.103202_bib20","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.tips.2024.05.006","article-title":"Targeting GPX4 in ferroptosis and cancer: chemical strategies and challenges","volume":"45","author":"Liu","year":"2024","journal-title":"Trends Pharm. Sci."},{"key":"10.1016\/j.tice.2025.103202_bib21","doi-asserted-by":"crossref","first-page":"1188365","DOI":"10.3389\/fimmu.2023.1188365","article-title":"Ferroptosis-mediated immune responses in cancer","volume":"14","author":"Qi","year":"2023","journal-title":"Front Immunol."},{"issue":"1","key":"10.1016\/j.tice.2025.103202_bib22","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s12964-020-00667-x","article-title":"Lactic acid promotes metastatic niche formation in bone metastasis of colorectal cancer","volume":"19","author":"Qian","year":"2021","journal-title":"Cell Commun. Signal"},{"key":"10.1016\/j.tice.2025.103202_bib23","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.freeradbiomed.2018.09.014","article-title":"Role of GPX4 in ferroptosis and its pharmacological implication","volume":"133","author":"Seibt","year":"2019","journal-title":"Free Radic. Biol. Med"},{"key":"10.1016\/j.tice.2025.103202_bib24","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2021.748925","article-title":"Prognostic and immunological role of key genes of ferroptosis in pan-cancer","volume":"9","author":"Shi","year":"2021","journal-title":"Front Cell Dev. Biol."},{"key":"10.1016\/j.tice.2025.103202_bib25","doi-asserted-by":"crossref","first-page":"1089918","DOI":"10.3389\/fendo.2022.1089918","article-title":"Lactate-related metabolic reprogramming and immune regulation in colorectal cancer","volume":"13","author":"Sun","year":"2022","journal-title":"Front Endocrinol. (Lausanne)"},{"issue":"1","key":"10.1016\/j.tice.2025.103202_bib26","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/s41392-023-01606-1","article-title":"Targeting ferroptosis opens new avenues for the development of novel therapeutics","volume":"8","author":"Sun","year":"2023","journal-title":"Signal Transduct. Target Ther."},{"issue":"2","key":"10.1016\/j.tice.2025.103202_bib27","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/s41422-020-00441-1","article-title":"Ferroptosis: molecular mechanisms and health implications","volume":"31","author":"Tang","year":"2021","journal-title":"Cell Res"},{"issue":"2","key":"10.1016\/j.tice.2025.103202_bib28","article-title":"Targeted xCT-mediated ferroptosis and protumoral polarization of macrophages is effective against HCC and enhances the efficacy of the Anti-PD-1\/L1 response","volume":"10","author":"Tang","year":"2023","journal-title":"Adv. Sci. (Weinh. )"},{"issue":"3","key":"10.1016\/j.tice.2025.103202_bib29","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.ccell.2023.02.016","article-title":"The evolving tumor microenvironment: from cancer initiation to metastatic outgrowth","volume":"41","author":"de Visser","year":"2023","journal-title":"Cancer Cell"},{"issue":"1","key":"10.1016\/j.tice.2025.103202_bib30","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41420-024-02037-9","article-title":"Ferroptosis: a double-edged sword","volume":"10","author":"Wang","year":"2024","journal-title":"Cell Death Discov."},{"issue":"10","key":"10.1016\/j.tice.2025.103202_bib31","doi-asserted-by":"crossref","first-page":"2621","DOI":"10.1080\/15548627.2023.2218764","article-title":"GPX4 in cell death, autophagy, and disease","volume":"19","author":"Xie","year":"2023","journal-title":"Autophagy"},{"issue":"11","key":"10.1016\/j.tice.2025.103202_bib32","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2021.109235","article-title":"The glutathione peroxidase Gpx4 prevents lipid peroxidation and ferroptosis to sustain Treg cell activation and suppression of antitumor immunity","volume":"35","author":"Xu","year":"2021","journal-title":"Cell Rep."},{"issue":"10-12","key":"10.1016\/j.tice.2025.103202_bib33","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1089\/ars.2021.0200","article-title":"miR-210 hypoxamiR in angiogenesis and diabetes","volume":"36","author":"Zaccagnini","year":"2022","journal-title":"Antioxid. Redox Signal"},{"key":"10.1016\/j.tice.2025.103202_bib34","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2022.108994","article-title":"The role of glycolysis and lactate in the induction of tumor-associated macrophages immunosuppressive phenotype","volume":"110","author":"Zhang","year":"2022","journal-title":"Int. Immunopharmacol."},{"issue":"1","key":"10.1016\/j.tice.2025.103202_bib35","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1080\/08830185.2021.1955876","article-title":"Lactic acid in macrophage polarization: the significant role in inflammation and cancer","volume":"41","author":"Zhou","year":"2022","journal-title":"Int. Rev. Immunol."},{"issue":"7","key":"10.1016\/j.tice.2025.103202_bib36","doi-asserted-by":"crossref","first-page":"203","DOI":"10.31083\/j.fbl2707203","article-title":"Targeting the macrophage-ferroptosis crosstalk: a novel insight into tumor immunotherapy","volume":"27","author":"Zhou","year":"2022","journal-title":"Front. Biosci. (Landmark Ed. )"},{"issue":"1","key":"10.1016\/j.tice.2025.103202_bib37","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1038\/s41467-019-09277-9","article-title":"A GPX4-dependent cancer cell state underlies the clear-cell morphology and confers sensitivity to ferroptosis","volume":"10","author":"Zou","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.tice.2025.103202_bib38","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.jcis.2024.03.001","article-title":"Lactic acid responsive sequential production of hydrogen peroxide and consumption of glutathione for enhanced ferroptosis tumor therapy","volume":"663","author":"Zou","year":"2024","journal-title":"J. Colloid Interface Sci."}],"container-title":["Tissue and Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0040816625004847?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0040816625004847?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T04:13:23Z","timestamp":1785298403000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0040816625004847"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":38,"alternative-id":["S0040816625004847"],"URL":"https:\/\/doi.org\/10.1016\/j.tice.2025.103202","relation":{},"ISSN":["0040-8166"],"issn-type":[{"value":"0040-8166","type":"print"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Lactic acid inhibits ferroptosis and promotes M2 macrophage polarization in colon cancer via GPX4 regulation","name":"articletitle","label":"Article Title"},{"value":"Tissue and Cell","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.tice.2025.103202","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"103202"}}