{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:24:14Z","timestamp":1791923054995,"version":"4.3.4"},"reference-count":55,"publisher":"American Society for Clinical Investigation","issue":"8","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"vor","delay-in-days":56,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the grants from the National Natural Science Foundation of China","award":["82103594,82273412,82372704"],"award-info":[{"award-number":["82103594,82273412,82372704"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,15]]},"abstract":"<jats:p>\n                    Tumor cells often employ many ways to restrain type I IFN signaling to evade immune surveillance. However, whether cellular amino acid metabolism regulates this process remains unclear, and its effects on antitumor immunity are relatively unexplored. Here, we found that asparagine inhibited IFN-I signaling and promoted immune escape in bladder cancer. Depletion of asparagine synthetase (ASNS) strongly limited in vivo tumor growth in a CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell\u2013dependent manner and boosted immunotherapy efficacy. Moreover, clinically approved L-asparaginase (ASNase),synergized with anti\u2013PD-1 therapy in suppressing tumor growth. Mechanistically, asparagine can directly bind to RIG-I and facilitate CBL-mediated RIG-I degradation, thereby suppressing IFN signaling and antitumor immune responses. Clinically, tumors with higher ASNS expression show decreased responsiveness to immune checkpoint inhibitor therapy. Together, our findings uncover asparagine as a natural metabolite to modulate RIG-I\u2013mediated IFN-I signaling, providing the basis for developing the combinatorial use of ASNase and anti\u2013PD-1 for bladder cancer.\n                  <\/jats:p>","DOI":"10.1172\/jci186648","type":"journal-article","created":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T12:00:17Z","timestamp":1739880017000},"source":"Crossref","is-referenced-by-count":24,"title":["Asparagine drives immune evasion in bladder cancer via RIG-I stability and type I IFN signaling"],"prefix":"10.1172","volume":"135","author":[{"given":"Wenjie","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Urology, The Third Medical Center and"},{"name":"Department of Urology Laboratory, Chinese PLA General Hospital, Beijing, China."},{"name":"Medical School of PLA, Beijing, 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