{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T11:43:02Z","timestamp":1774698182608,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Isobutyric acid (IBA), a short\u2010chain fatty acid, has been unequivocally demonstrated to exert significant influence on the progression of colorectal cancer (CRC). Nevertheless, a comprehensive understanding of its intricate regulatory mechanisms remains elusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Employing advanced techniques such as western blot, RT\u2010qPCR, and flow cytometry, we systematically investigated the impact of IBA on the expression of PD\u2010L1 in CRC cells. Concurrently, employing RNA silencing technology and small\u2010molecule inhibitors, we delved into the molecular intricacies underlying the regulatory axis of IBA involving ROCK1\/c\u2010Myc\/PD\u2010L1. Furthermore, through flow cytometry analysis, we examined the alterations in the tumor immune microenvironment following anti\u2010PD\u2010L1 antibody therapy in a murine tumor model treated with IBA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Elevated levels of IBA were found to robustly activate PD\u2010L1 expression in CRC cells both in\u00a0vitro and in\u00a0vivo, concomitantly reshaping the tumor immune microenvironment. Subsequent mechanistic investigations unveiled that IBA, through its interaction and activation of ROCK1, promotes the activation of c\u2010Myc, thereby enhancing the transcription of PD\u2010L1. Silencing of ROCK1 and application of ROCK1 inhibitors effectively reversed the regulatory effects of IBA on PD\u2010L1. Additionally, IBA inhibited the activity of infiltrating CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, resulting in diminished antitumor immunity and attenuating the sensitivity to anti\u2010PD\u2010L1 therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study elucidates a novel mechanism by which IBA inhibits the sensitivity of CRC to anti\u2010PD\u2010L1 antibody therapy. Emphasizing IBA and its downstream pathways as potential therapeutic targets for immune therapy resistance mechanisms, our findings provide a novel theoretical foundation for overcoming immune therapy resistance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.70397","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T06:12:17Z","timestamp":1730873537000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Isobutyric Acid Promotes Immune Evasion in Colorectal Cancer via Increased\n                    <scp>PD<\/scp>\n                    \u2010\n                    <scp>L1<\/scp>\n                    Expression"],"prefix":"10.1002","volume":"13","author":[{"given":"Qiuhua","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery Guangxi Medical University Cancer Hospital, Guangxi Medical University  Nanning Guangxi P.R. 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