{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T20:45:52Z","timestamp":1774903552662,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T00:00:00Z","timestamp":1688342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Chronic inflammation is considered the most critical predisposing factor of hepatocellular carcinoma (HCC), with inflammatory cell heterogeneity, hepatic fibrosis accumulation, and abnormal vascular proliferation as prominent features of the HCC tumor microenvironment (TME). Cancer\u2010associated fibroblasts (CAFs) play a key role in HCC TME remodeling. Therefore, the level of abundance of CAFs may significantly affect the prognosis and outcome in HCC patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Unsupervised clustering was performed based on 39 genes related to CAFs in HCC identified by single\u2010cell RNA sequencing\u00a0data. Patients of bulk RNA were grouped into CAF low abundance cluster and high abundance clusters. Subsequently, prognosis, immune infiltration landscape, metabolism, and treatment response between the two clusters were investigated and validated by immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients in the CAF high cluster had a higher level of inflammatory cell infiltration, a more significant immunosuppressive microenvironment, and a significantly worse prognosis than those in the low cluster. At the metabolic level, the CAF high cluster had lower levels of aerobic oxidation and higher angiogenic scores. Drug treatment response prediction indicated that the CAF high cluster could have a better response to PD\u20101 inhibitors and conventional chemotherapeutic agents for HCC such as anti\u2010angiogenic drugs, whereas CAF low cluster may be more sensitive to transarterial chemoembolization treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study not only revealed the TME characteristics of HCC with the difference in CAF abundance but also further confirmed that the combination therapy of PD\u20101 inhibitors and anti\u2010angiogenic drugs may be more valuable for patients with high CAF abundance.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.34935","type":"journal-article","created":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T05:20:52Z","timestamp":1688361652000},"page":"3405-3416","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Cancer\u2010associated fibroblasts contribute to the immunosuppressive landscape and influence the efficacy of\u00a0the combination therapy of PD\u20101 inhibitors and antiangiogenic agents in hepatocellular carcinoma"],"prefix":"10.1002","volume":"129","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1119-3744","authenticated-orcid":false,"given":"Qiurui","family":"Chen","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Biotechnology Drug Candidate Research School of Life Sciences and Biopharmaceutics Guangdong Pharmaceutical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuejia","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Biotechnology Drug Candidate Research School of Life Sciences and Biopharmaceutics Guangdong Pharmaceutical University  Guangzhou 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