{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T16:08:30Z","timestamp":1790352510490,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82372934"],"award-info":[{"award-number":["82372934"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Lactate is a vital metabolite in cancer, significantly impacting tumor progression, metastasis, and overall survival. The CD147\u2013monocarboxylate transporter 1 (MCT1) complex, a major lactate transporter, has emerged as a promising therapeutic target. However, no effective protein\u2013protein interaction (PPI) inhibitors targeting the CD147\u2013MCT1 complex have been identified. In this study, we found that the small\u2010molecule inhibitor crizotinib effectively disrupts the CD147\u2013MCT1 interaction, leading to reduced lactate secretion from melanoma cells and decreased lactate uptake by macrophages. In vivo studies demonstrated that crizotinib treatment significantly suppressed tumor growth and enhanced responsiveness to immune checkpoint blockade therapy. Flow cytometry revealed that this metabolic intervention inhibits M2 polarization and reshapes the tumor immune microenvironment. Transcriptomic analysis further revealed that lactate induces C\u2010X\u2010C motif chemokine ligand 13 (CXCL13) expression in macrophages, which enhances melanoma invasiveness and impairs immune cell\u2010mediated cytotoxicity. Importantly, crizotinib suppresses CXCL13 expression by blocking lactate\u2010driven histone lactylation, thereby reversing the transcriptional reprogramming induced by lactate, as evidenced by reduced histone H3 lysine 18 lactylation (H3K18la) enrichment at the CXCL13 promoter. Taken together, these findings provide new insights into targeting metabolic\u2010immune crosstalk and highlight the value of disrupting CD147\u2013MCT1 interactions to improve immunotherapeutic responses in patients with melanoma.<\/jats:p>","DOI":"10.1002\/mco2.70286","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T08:09:23Z","timestamp":1753085363000},"source":"Crossref","is-referenced-by-count":11,"title":["Crizotinib: A Novel Strategy to Reverse Immunosuppression in Melanoma by Targeting Lactate Transport"],"prefix":"10.1002","volume":"6","author":[{"given":"Zhe","family":"Zhou","sequence":"first","affiliation":[{"name":"The Department of Dermatology Xiangya Hospital Central South University  Changsha China"},{"name":"Furong Laboratory  Changsha China"},{"name":"Hunan Key Laboratory of Skin Cancer and Psoriasis Xiangya Hospital Central South University  Changsha China"},{"name":"Hunan Engineering Research Center of Skin Health and Disease Xiangya Hospital Central South University  Changsha China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Department of Dermatology Xiangya Hospital Central South University  Changsha China"},{"name":"Furong Laboratory  Changsha China"},{"name":"Hunan Key Laboratory of Skin Cancer and Psoriasis Xiangya Hospital Central South University  Changsha China"},{"name":"Hunan Engineering Research Center of Skin Health and Disease Xiangya Hospital Central South University  Changsha China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susi","family":"Zhu","sequence":"additional","affiliation":[{"name":"The Department of Dermatology Xiangya Hospital Central South University  Changsha China"},{"name":"Furong Laboratory  Changsha China"},{"name":"Hunan Key Laboratory of Skin Cancer and Psoriasis Xiangya Hospital Central South University  Changsha China"},{"name":"Hunan Engineering Research Center of Skin Health and Disease Xiangya Hospital Central South University  Changsha China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waner","family":"Liu","sequence":"additional","affiliation":[{"name":"The Department of Dermatology Xiangya Hospital Central South University  Changsha China"},{"name":"Furong Laboratory  Changsha China"},{"name":"Hunan Key Laboratory of Skin Cancer and Psoriasis Xiangya Hospital Central South University  Changsha China"},{"name":"Hunan Engineering Research Center of Skin Health and Disease Xiangya Hospital Central South University  Changsha China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeye","family":"Guo","sequence":"additional","affiliation":[{"name":"The Department of Dermatology Xiangya Hospital Central South University  Changsha China"},{"name":"Furong Laboratory  Changsha China"},{"name":"Hunan Key Laboratory of Skin Cancer and Psoriasis Xiangya Hospital Central South University  Changsha China"},{"name":"Hunan Engineering Research Center of Skin Health and Disease Xiangya Hospital Central South University  Changsha China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Xiong","sequence":"additional","affiliation":[{"name":"The Department of Dermatology Xiangya Hospital Central South University  Changsha China"},{"name":"Furong Laboratory  Changsha China"},{"name":"Hunan Key Laboratory of Skin Cancer and Psoriasis Xiangya Hospital Central South University  Changsha China"},{"name":"Hunan Engineering Research Center of Skin Health and Disease Xiangya Hospital Central South University  Changsha China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7104-5490","authenticated-orcid":false,"given":"Cong","family":"Peng","sequence":"additional","affiliation":[{"name":"The Department of Dermatology Xiangya Hospital Central South University  Changsha China"},{"name":"Furong Laboratory  Changsha China"},{"name":"Hunan Key Laboratory of Skin Cancer and Psoriasis Xiangya Hospital Central South University  Changsha China"},{"name":"Hunan Engineering Research Center of Skin Health and Disease Xiangya Hospital Central South University  Changsha China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Chen","sequence":"additional","affiliation":[{"name":"The Department of Dermatology Xiangya Hospital Central South University  Changsha China"},{"name":"Furong Laboratory  Changsha China"},{"name":"Hunan Key Laboratory of Skin Cancer and Psoriasis Xiangya Hospital Central South University  Changsha China"},{"name":"Hunan Engineering Research Center of Skin Health and Disease Xiangya Hospital Central South University  Changsha China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3038"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202115343"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24097986"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2022.01.001"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2022.10.005"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adg2697"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-023-01061-6"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-019-0760-3"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.53749"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2102434118"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1678-1"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-021-00841-9"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.04.006"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202000549"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-13-2034"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2023.01.007"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-022-02427-w"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-00570-y"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-022-01617-x"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2008.07.034"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.15.3896"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3048"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aax2277"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103627"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-17-1253"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox13070801"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-019-0717-x"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-2263"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2213093"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022016040"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe2023326"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.27385"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-019-0758-y"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2017.01.031"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12010091"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.08.012"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.44321"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112945"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2027187"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0406-2"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcis.2024.01.129"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1918986117"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01267-2"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.587913"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.122.320488"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2021.07.009"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-003890"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-020-00991-2"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2017.1290034"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00598-0"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-024-01985-9"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI187024"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-021-02308-z"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.113688"}],"container-title":["MedComm"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mco2.70286","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,16]],"date-time":"2025-08-16T06:15:18Z","timestamp":1755324918000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mco2.70286"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,21]]},"references-count":54,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/mco2.70286"],"URL":"https:\/\/doi.org\/10.1002\/mco2.70286","archive":["Portico"],"relation":{},"ISSN":["2688-2663","2688-2663"],"issn-type":[{"value":"2688-2663","type":"print"},{"value":"2688-2663","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,21]]},"article-number":"e70286"}}