{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T19:26:31Z","timestamp":1793733991655,"version":"4.6.1"},"reference-count":49,"publisher":"National Academy of Sciences","issue":"19","license":[{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA234128"],"award-info":[{"award-number":["R01CA234128"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["U01AA027681"],"award-info":[{"award-number":["U01AA027681"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,5,9]]},"abstract":"<jats:p>\n                    Although viral hepatocellular carcinoma (HCC) is declining, nonviral HCC, which often is the end stage of nonalcoholic or alcoholic steatohepatitis (NASH, ASH), is on an upward trajectory. Immune checkpoint inhibitors (ICIs) that block the T cell inhibitory receptor PD-1 were approved for treatment of all HCC types. However, only a minority of HCC patients show a robust and sustained response to PD-1 blockade, calling for improved understanding of factors that negatively impact response rate and duration and the discovery of new adjuvant treatments that enhance ICI responsiveness. Using a mouse model of NASH-driven HCC, we identified peritumoral fibrosis as a potential obstacle to T cell\u2013mediated tumor regression and postulated that antifibrotic medications may increase ICI responsiveness. We now show that the angiotensin II receptor inhibitor losartan, a commonly prescribed and safe antihypertensive drug, reduced liver and peritumoral fibrosis and substantially enhanced anti-PD-1-induced tumor regression. Although losartan did not potentiate T cell reinvigoration, it substantially enhanced HCC infiltration by effector CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells compared to PD-1 blockade alone. The beneficial effects of losartan correlated with blunted TGF-\u03b2 receptor signaling, reduced collagen deposition, and depletion of immunosuppressive fibroblasts.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2300706120","type":"journal-article","created":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T15:11:27Z","timestamp":1682953887000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":49,"title":["Angiotensin II receptor inhibition ameliorates liver fibrosis and enhances hepatocellular carcinoma infiltration by effector T cells"],"prefix":"10.1073","volume":"120","author":[{"given":"Li","family":"Gu","sequence":"first","affiliation":[{"name":"Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Pathology, School of Medicine, University of California San Diego, San Diego, CA 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