{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T11:17:29Z","timestamp":1784546249444,"version":"3.55.0"},"reference-count":29,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,13]],"date-time":"2025-04-13T00:00:00Z","timestamp":1744502400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82272978"],"award-info":[{"award-number":["82272978"]}]},{"name":"National Natural Science Foundation of China","award":["2021CFB484"],"award-info":[{"award-number":["2021CFB484"]}]},{"name":"National Natural Science Foundation of China","award":["2024KZL07"],"award-info":[{"award-number":["2024KZL07"]}]},{"name":"Natural Science Foundation Project of Hubei Province","award":["82272978"],"award-info":[{"award-number":["82272978"]}]},{"name":"Natural Science Foundation Project of Hubei Province","award":["2021CFB484"],"award-info":[{"award-number":["2021CFB484"]}]},{"name":"Natural Science Foundation Project of Hubei Province","award":["2024KZL07"],"award-info":[{"award-number":["2024KZL07"]}]},{"name":"Open Foundation of Hubei Province Key Laboratory of Tumor Microenvironment and Immunotherapy","award":["82272978"],"award-info":[{"award-number":["82272978"]}]},{"name":"Open Foundation of Hubei Province Key Laboratory of Tumor Microenvironment and Immunotherapy","award":["2021CFB484"],"award-info":[{"award-number":["2021CFB484"]}]},{"name":"Open Foundation of Hubei Province Key Laboratory of Tumor Microenvironment and Immunotherapy","award":["2024KZL07"],"award-info":[{"award-number":["2024KZL07"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Hepatocellular carcinoma (HCC) is a prevalent and highly lethal form of liver cancer, with limited effective treatment options, particularly in the advanced stages. Immunotherapy using PD-1 inhibitors has emerged as a promising treatment modality, yet a substantial proportion of patients exhibit resistance or fail to respond to such therapies. This study aimed to elucidate the role of G0\/G1 Switch 2 (G0S2) in regulating PD-L1 expression in monocytes within the HCC tumor microenvironment and to investigate its impact on the efficacy of PD-1 inhibitors. Methods: Gene expression data among HCC patients treated with PD-1 inhibitors were obtained from the HCC single-cell sequencing database; immunohistochemistry was performed to detect G0S2 expression in liver cancer tissues and adjacent non-tumorous tissues of HCC patients; flow cytometry was utilized to analyze the expression of G0S2, PD-L1, CD206, and CD14 in PBMCs from HCC patients; and CD8+T cell proliferation and IFN-\u03b3 secretion were used to evaluate the impact of G0S2 knockdown. Results: Utilizing single-cell sequencing data from HCC patients, we identified that G0S2 expression was significantly elevated in the non-responders (NR) compared to responders (R) to PD-1 inhibitor therapy. The immunohistochemical analysis confirmed higher levels of G0S2 in HCC tumor tissues and adjacent non-tumorous tissues, while the flow cytometry revealed the increased expression of G0S2, PD-L1, and CD206 in peripheral blood mononuclear cells (PBMCs) from NR patients compared to R patients and healthy controls. The functional experiments involving the knockdown of G0S2 in the THP-1 monocyte cell line resulted in a significant reduction in PD-L1 expression and a concomitant increase in CD8+T cell proliferation and IFN-\u03b3 production. Conclusions: These findings indicate that G0S2 facilitates the upregulation of PD-L1 in monocytes, thereby suppressing T cell activity and contributing to resistance against PD-1 inhibitors in HCC. The high expression of G0S2 in peripheral blood monocytes offers a non-invasive and easily detectable biomarker for predicting the efficacy of PD-1 inhibitor therapy. Consequently, targeting G0S2 may enhance the responsiveness to immunotherapy in HCC patients, providing a new avenue for optimizing treatment strategies and improving patient outcomes.<\/jats:p>","DOI":"10.3390\/genes16040448","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T07:42:01Z","timestamp":1744616521000},"page":"448","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["G0S2 Promotes PD-L1 Expression in Monocytes and Influences the Efficacy of PD-1 Inhibitors in Hepatocellular Carcinoma"],"prefix":"10.3390","volume":"16","author":[{"given":"Xuanshuang","family":"Du","sequence":"first","affiliation":[{"name":"Department of Immunology, Taikang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Immunology, Taikang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujuan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Immunology, Taikang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, TaiKang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanying","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pathology, TaiKang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengling","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Immunology, Taikang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4144-3065","authenticated-orcid":false,"given":"Hongyan","family":"Wu","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang 443002, China"},{"name":"College of Basic Medicine, China Three Gorges University, Yichang 443002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7095-1344","authenticated-orcid":false,"given":"Min","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Immunology, Taikang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s41571-021-00573-2","article-title":"Finn Immunotherapies for hepatocellular carcinoma","volume":"19","author":"Llovet","year":"2022","journal-title":"Nat. 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