{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T23:27:00Z","timestamp":1792279620433,"version":"4.4.0"},"reference-count":188,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":28,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"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":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitors (ICIs) targeting the PD\u20101\/PD\u2010L1 pathway have revolutionized cancer immunotherapy, yet their clinical benefit is constrained by variable response rates and immune\u2010related adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This review systematically analyzes the molecular mechanisms by which key gut microbiota\u2010derived metabolites\u2014including short\u2010chain fatty acids (SCFAs), tryptophan metabolites, and bile acids\u2014modulate the PD\u20101\/PD\u2010L1 axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials &amp; Methods<\/jats:title>\n                    <jats:p>We synthesized and evaluated peer\u2010reviewed preclinical and clinical studies published over the past decade, focusing on metabolite\u2013immune interactions, biomarker validation, and combinatorial intervention strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The summarized evidence demonstrates that these metabolites exert significant influences on the tumor microenvironment, enhance T\u2010cell effector functions, and reshape immune tolerance, thereby affecting ICI responsiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>We critically assess the predictive value of microbiota metabolites as potential biomarkers and review current progress in probiotic supplementation, fecal microbiota transplantation, and metabolite\u2010based combination therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Despite promising translational prospects, several challenges\u2014including inter\u2010individual variability, lack of standardized protocols, and mechanistic gaps\u2014remain to be addressed. Future directions should prioritize large\u2010scale longitudinal studies and refined intervention designs to facilitate the clinical integration of microbiota\u2010guided strategies, ultimately improving the precision and efficacy of cancer immunotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/iid3.70492","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T11:23:43Z","timestamp":1785324223000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Regulation of PD\u20101PD\u2010L1 Immune Checkpoints by Gut Microbiota Metabolites and Their Clinical Translational Research: A Review"],"prefix":"10.1002","volume":"14","author":[{"given":"Xuanyou","family":"Fang","sequence":"first","affiliation":[{"name":"Xiaolan Clinical Institute of Shantou University Medical College Zhongshan Guangdong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Yuan","sequence":"additional","affiliation":[{"name":"Xiaolan Clinical Institute of Shantou University Medical College Zhongshan Guangdong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2468-2914","authenticated-orcid":false,"given":"Weijian","family":"Mai","sequence":"additional","affiliation":[{"name":"Xiaolan Clinical Institute of Shantou University Medical College Zhongshan Guangdong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"issue":"7","key":"e_1_2_18_2_1","doi-asserted-by":"crossref","DOI":"10.1002\/iid3.1263","article-title":"Potential Mechanisms and Targeting Strategies of the Gut Microbiota in Antitumor Immunity and Immunotherapy","volume":"12","author":"Yin Q.","year":"2024","journal-title":"Immunity, Inflammation and Disease"},{"issue":"8","key":"e_1_2_18_3_1","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.3390\/life12081229","article-title":"Emerging Immune\u2010Monitoring System for Immune Checkpoint Inhibitors","volume":"12","author":"Hamada K.","year":"2022","journal-title":"Life"},{"issue":"1","key":"e_1_2_18_4_1","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1186\/s13046-025-03519-z","article-title":"Immunotherapy Resistance in Non\u2010Small Cell Lung Cancer: From Mechanisms to Therapeutic Opportunities","volume":"44","author":"Wang H.","year":"2025","journal-title":"Journal of Experimental & Clinical Cancer Research: CR"},{"issue":"9","key":"e_1_2_18_5_1","first-page":"1096","article-title":"[Association Between Immunotherapy With Immune Checkpoint Inhibitors(Anti\u2010PD\u20101 Antibodies)And Intestinal Microbiota]","volume":"48","author":"Ozaki Y.","year":"2021","journal-title":"Gan to kagaku ryoho. 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