{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T19:29:06Z","timestamp":1791660546357,"version":"4.3.4"},"reference-count":79,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:00:00Z","timestamp":1678838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82100656"],"award-info":[{"award-number":["82100656"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Hepatocellular carcinoma (HCC), the third most prevalent cause of cancer-related death, is a frequent primary liver cancer with a high rate of morbidity and mortality. T-cell depletion (TEX) is a progressive decline in T-cell function due to continuous stimulation of the TCR in the presence of sustained antigen exposure. Numerous studies have shown that TEX plays an essential role in the antitumor immune process and is significantly associated with patient prognosis. Hence, it is important to gain insight into the potential role of T cell depletion in the tumor microenvironment. The purpose of this study was to develop a trustworthy TEX-based signature using single-cell RNA-seq (scRNA-seq) and high-throughput RNA sequencing, opening up new avenues for evaluating the prognosis and immunotherapeutic response of HCC patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) databases were used to download RNA-seq information for HCC patients. The 10x scRNA-seq. data of HCC were downloaded from GSE166635, and UMAP was used for clustering descending, and subgroup identification. TEX-related genes were identified by gene set variance analysis (GSVA) and weighted gene correlation network analysis (WGCNA). Afterward, we established a prognostic TEX signature using LASSO-Cox analysis. External validation was performed in the ICGC cohort. Immunotherapy response was assessed by the IMvigor210, GSE78220, GSE79671, and GSE91061cohorts. In addition, differences in mutational landscape and chemotherapy sensitivity between different risk groups were investigated. Finally, the differential expression of TEX genes was verified by qRT-PCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Result<\/jats:title><jats:p>11 TEX genes were thought to be highly predictive of the prognosis of HCC and substantially related to HCC prognosis. Patients in the low-risk group had a greater overall survival rate than those in the high-risk group, according to multivariate analysis, which also revealed that the model was an independent predictor of HCC. The predictive efficacy of columnar maps created from clinical features and risk scores was strong.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>TEX signature and column line plots showed good predictive performance, providing a new perspective for assessing pre-immune efficacy, which will be useful for future precision immuno-oncology studies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1137025","type":"journal-article","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T04:43:15Z","timestamp":1678855395000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":136,"title":["T-cell exhaustion signatures characterize the immune landscape and predict HCC prognosis via integrating single-cell RNA-seq and bulk RNA-sequencing"],"prefix":"10.3389","volume":"14","author":[{"given":"Hao","family":"Chi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songyun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinrui","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaoge","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xixi","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guobin","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijia","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinqiu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.08.017","article-title":"Advances in molecular classification and precision oncology in hepatocellular carcinoma","volume":"72","author":"Rebouissou","year":"2020","journal-title":"J Hepatol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J Clin"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.08.025","article-title":"Epidemiology and surveillance for hepatocellular carcinoma: New trends","volume":"72","author":"Singal","year":"2020","journal-title":"J Hepatol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.07.033","article-title":"Nafld and liver transplantation: Current burden and expected challenges","volume":"65","author":"Pais","year":"2016","journal-title":"J Hepatol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-321702","article-title":"Immunotherapy for advanced hepatocellular carcinoma: A focus on special subgroups","volume":"70","author":"Pinter","year":"2021","journal-title":"Gut"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2035","article-title":"T Cell exhaustion","volume":"12","author":"Wherry","year":"2011","journal-title":"Nat Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.08.021","article-title":"Network analysis reveals centrally connected genes and pathways involved in Cd8+ T cell exhaustion versus memory","volume":"37","author":"Doering","year":"2012","journal-title":"Immunity"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/362758a0","article-title":"Virus persistence in acutely infected immunocompetent mice by exhaustion of antiviral cytotoxic effector T cells","volume":"362","author":"Moskophidis","year":"1993","journal-title":"Nature"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nature05115","article-title":"Pd-1 expression on hiv-specific T cells is associated with T-cell exhaustion and disease progression","volume":"443","author":"Day","year":"2006","journal-title":"Nature"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nri3862","article-title":"Molecular and cellular insights into T cell exhaustion","volume":"15","author":"Wherry","year":"2015","journal-title":"Nat Rev Immunol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1186\/s12885-022-10305-z","article-title":"Expression of hub genes of endothelial cells in glioblastoma-a prognostic model for gbm patients integrating single-cell rna sequencing and bulk rna sequencing","volume":"22","author":"Zhao","year":"2022","journal-title":"BMC Cancer"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-041015-055318","article-title":"Cd8 T cell exhaustion during chronic viral infection and cancer","volume":"37","author":"McLane","year":"2019","journal-title":"Annu Rev Immunol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"677","DOI":"10.3390\/ph14070677","article-title":"Hacking pancreatic cancer: Present and future of personalized medicine","volume":"14","author":"Di Federico","year":"2021","journal-title":"Pharm (Basel)"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1101\/gr.239244.118","article-title":"Maftools: Efficient and comprehensive analysis of somatic variants in cancer","volume":"28","author":"Mayakonda","year":"2018","journal-title":"Genome Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/advs.201902880","article-title":"Immucellai: A unique method for comprehensive T-cell subsets abundance prediction and its application in cancer immunotherapy","volume":"7","author":"Miao","year":"2020","journal-title":"Adv Sci (Weinh)"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7","article-title":"Gsva: Gene set variation analysis for microarray and rna-seq data","volume":"14","author":"H\u00e4nzelmann","year":"2013","journal-title":"BMC Bioinf"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.104207","article-title":"Pan-cancer landscape of T-cell exhaustion heterogeneity within the tumor microenvironment revealed a progressive roadmap of hierarchical dysfunction associated with prognosis and therapeutic efficacy","volume":"83","author":"Zhang","year":"2022","journal-title":"EBioMedicine"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-559","article-title":"Wgcna: An r package for weighted correlation network analysis","volume":"9","author":"Langfelder","year":"2008","journal-title":"BMC Bioinf"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1038\/s41467-021-21246-9","article-title":"Inference and analysis of cell-cell communication using cellchat","volume":"12","author":"Jin","year":"2021","journal-title":"Nat Commun"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.TIR120.002155","article-title":"Reactomegsa - efficient multi-omics comparative pathway analysis","volume":"19","author":"Griss","year":"2020","journal-title":"Mol Cell Proteomics"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0276-y","article-title":"Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage","volume":"20","author":"Aran","year":"2019","journal-title":"Nat Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.05.002","article-title":"Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets","volume":"161","author":"Macosko","year":"2015","journal-title":"Cell"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/nature22367","article-title":"Chromatin states define tumour-specific T cell dysfunction and reprogramming","volume":"545","author":"Philip","year":"2017","journal-title":"Nature"},{"key":"B24","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1038\/nature23306","article-title":"Integrative clinical genomics of metastatic cancer","volume":"548","author":"Robinson","year":"2017","journal-title":"Nature"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10582","article-title":"Melanoma-specific mhc-ii expression represents a tumour-autonomous phenotype and predicts response to anti-Pd-1\/Pd-L1 therapy","volume":"7","author":"Johnson","year":"2016","journal-title":"Nat Commun"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.1010044","article-title":"Identification and validation of neurotrophic factor-related genes signature in hnscc to predict survival and immune landscapes","volume":"13","author":"Peng","year":"2022","journal-title":"Front Genet"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/1759-7714.14217","article-title":"Formation, contents, functions of exosomes and their potential in lung cancer diagnostics and therapeutics","volume":"12","author":"Xia","year":"2021","journal-title":"Thorac Cancer"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/1802706","article-title":"Identification of potential biomarkers for progression and prognosis of bladder cancer by comprehensive bioinformatics analysis","volume":"2022","author":"Tan","year":"2022","journal-title":"J Oncol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.Cd-18-0367","article-title":"Fundamental mechanisms of immune checkpoint blockade therapy","volume":"8","author":"Wei","year":"2018","journal-title":"Cancer Discovery"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-022-00689-z","article-title":"Clinical implications of T cell exhaustion for cancer immunotherapy","volume":"19","author":"Chow","year":"2022","journal-title":"Nat Rev Clin Oncol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.783335","article-title":"Overexpression of pd-L1 is an independent predictor for recurrence in hcc patients who receive sorafenib treatment after surgical resection","volume":"11","author":"Tan","year":"2021","journal-title":"Front Oncol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1080\/19336918.2022.2103925","article-title":"Fluid shear stress induces cell migration Via rhoa-Yap1-Autophagy pathway in liver cancer stem cells","volume":"16","author":"Yan","year":"2022","journal-title":"Cell Adh Migr"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.28019","article-title":"Therapeutic advances for patients with intermediate hepatocellular carcinoma","volume":"234","author":"Sun","year":"2019","journal-title":"J Cell Physiol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209548","article-title":"New aspects of diagnosis and therapy of hepatocellular carcinoma","volume":"25","author":"Bruix","year":"2006","journal-title":"Oncogene"},{"key":"B35","doi-asserted-by":"publisher","first-page":"466","DOI":"10.21037\/atm.2020.03.92","article-title":"High Rps11 level in hepatocellular carcinoma associates with poor prognosis after curative resection","volume":"8","author":"Zhou","year":"2020","journal-title":"Ann Transl Med"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.864051","article-title":"Prc1 and Racgap1 are diagnostic biomarkers of early hcc and Prc1 drives self-renewal of liver cancer stem cells","volume":"10","author":"Liao","year":"2022","journal-title":"Front Cell Dev Biol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.1038\/s41467-021-21804-1","article-title":"Tumor methionine metabolism drives T-cell exhaustion in hepatocellular carcinoma","volume":"12","author":"Hung","year":"2021","journal-title":"Nat Commun"},{"key":"B38","doi-asserted-by":"publisher","first-page":"51","DOI":"10.2147\/ott.S237399","article-title":"Up-regulated Ccdc34 contributes to the proliferation and metastasis of hepatocellular carcinoma","volume":"13","author":"Lin","year":"2020","journal-title":"Onco Targets Ther"},{"key":"B39","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.ejmp.2021.02.013","article-title":"A deep survival interpretable radiomics model of hepatocellular carcinoma patients","volume":"82","author":"Wei","year":"2021","journal-title":"Phys Med"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.2147\/jhc.S325629","article-title":"Serum Klkb1 as a potential prognostic biomarker for hepatocellular carcinoma based on data-independent acquisition and parallel reaction monitoring","volume":"8","author":"Che","year":"2021","journal-title":"J Hepatocell Carcinoma"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/6509028","article-title":"Sortilin 1 promotes hepatocellular carcinoma cell proliferation and migration by regulating immune cell infiltration","volume":"2022","author":"Gao","year":"2022","journal-title":"J Oncol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/nri3790","article-title":"Clinical blockade of Pd1 and Lag3\u2013potential mechanisms of action","volume":"15","author":"Nguyen","year":"2015","journal-title":"Nat Rev Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2015.02.008","article-title":"Overcoming T cell exhaustion in infection and cancer","volume":"36","author":"Pauken","year":"2015","journal-title":"Trends Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/nature04444","article-title":"Restoring function in exhausted Cd8 T cells during chronic viral infection","volume":"439","author":"Barber","year":"2006","journal-title":"Nature"},{"key":"B45","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.it.2013.10.001","article-title":"Tolerance and exhaustion: Defining mechanisms of T cell dysfunction","volume":"35","author":"Schietinger","year":"2014","journal-title":"Trends Immunol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1093\/intimm\/dxs074","article-title":"Tak1 contributes to the enhanced responsiveness of Ltb(4)-treated neutrophils to toll-like receptor ligands","volume":"24","author":"Gaudreault","year":"2012","journal-title":"Int Immunol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90574-a","article-title":"Lymphotoxin beta, a novel member of the tnf family that forms a heteromeric complex with lymphotoxin on the cell surface","volume":"72","author":"Browning","year":"1993","journal-title":"Cell"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003234","article-title":"Lymphotoxin signaling is initiated by the viral polymerase in hcv-linked tumorigenesis","volume":"9","author":"Simonin","year":"2013","journal-title":"PloS Pathog"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1080\/2162402x.2017.1404214","article-title":"Ox40 expression in hepatocellular carcinoma is associated with a distinct immune microenvironment, specific mutation signature, and poor prognosis","volume":"7","author":"Xie","year":"2018","journal-title":"Oncoimmunology"},{"key":"B50","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1158\/1078-0432.Ccr-21-0845","article-title":"Open-label, dose-escalation study of the Ox40 agonist ivuxolimab in patients with locally advanced or metastatic cancers","volume":"28","author":"Diab","year":"2022","journal-title":"Clin Cancer Res"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3109\/07357900902849640","article-title":"Advances in thymosin Beta10 research: Differential expression, molecular mechanisms, and clinical implications in cancer and other conditions","volume":"27","author":"Sribenja","year":"2009","journal-title":"Cancer Invest"},{"key":"B52","doi-asserted-by":"publisher","first-page":"BSR20182355","DOI":"10.1042\/bsr20182355","article-title":"Thymosin B 10 is overexpressed and associated with unfavorable prognosis in hepatocellular carcinoma","volume":"39","author":"Song","year":"2019","journal-title":"Biosci Rep"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1080\/2162402x.2022.2141011","article-title":"Tbc1d10c is a selective, constitutive suppressor of the Cd8 T-cell anti-tumor response","volume":"11","author":"Cohen","year":"2022","journal-title":"Oncoimmunology"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.Can-05-4463","article-title":"Tumor cell-derived and macrophage-derived cathepsin b promotes progression and lung metastasis of mammary cancer","volume":"66","author":"Vasiljeva","year":"2006","journal-title":"Cancer Res"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1101\/gad.224899.113","article-title":"Cathepsin c is a tissue-specific regulator of squamous carcinogenesis","volume":"27","author":"Ruffell","year":"2013","journal-title":"Genes Dev"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(08)70172-4","article-title":"Second-hand smoke and human lung cancer","volume":"9","author":"Besaratinia","year":"2008","journal-title":"Lancet Oncol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.1058931","article-title":"Cancer informatics analysis indicates high Chac2 associated with unfavorable prognosis in breast cancer","volume":"12","author":"Chand","year":"2022","journal-title":"Front Oncol"},{"key":"B58","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1053\/j.gastro.2015.05.061","article-title":"Genetic landscape and biomarkers of hepatocellular carcinoma","volume":"149","author":"Zucman-Rossi","year":"2015","journal-title":"Gastroenterology"},{"key":"B59","doi-asserted-by":"publisher","first-page":"367","DOI":"10.3390\/cancers10100367","article-title":"Molecular scoring of hepatocellular carcinoma for predicting metastatic recurrence and requirements of systemic chemotherapy","volume":"10","author":"Nishida","year":"2018","journal-title":"Cancers (Basel)"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.734287","article-title":"Single-cell rna sequencing reveals the role of phosphorylation-related genes in hepatocellular carcinoma stem cells","volume":"9","author":"Yao","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0249174","article-title":"A panel of 8-lncrna predicts prognosis of breast cancer patients and migration of breast cancer cells","volume":"16","author":"Zhu","year":"2021","journal-title":"PloS One"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2013.00114","article-title":"Colorectal cancer: Molecular mutations and polymorphisms","volume":"3","author":"Sameer","year":"2013","journal-title":"Front Oncol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1200\/jco.18.01798","article-title":"Mutational analysis of patients with colorectal cancer in Calgb\/Swog 80405 identifies new roles of microsatellite instability and tumor mutational burden for patient outcome","volume":"37","author":"Innocenti","year":"2019","journal-title":"J Clin Oncol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.10.001","article-title":"The challenges of tumor mutational burden as an immunotherapy biomarker","volume":"39","author":"Jardim","year":"2021","journal-title":"Cancer Cell"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.989779","article-title":"Clinical neutrophil-associated genes as reliable predictors of hepatocellular carcinoma","volume":"13","author":"Song","year":"2022","journal-title":"Front Genet"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1002\/jso.25859","article-title":"Prognostic role of tumor mutation burden in hepatocellular carcinoma after radical hepatectomy","volume":"121","author":"Cai","year":"2020","journal-title":"J Surg Oncol"},{"key":"B67","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.3390\/cancers11091375","article-title":"The immune microenvironment of breast cancer progression","volume":"11","author":"Tower","year":"2019","journal-title":"Cancers (Basel)"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1080\/2162402x.2019.1571388","article-title":"Landscape of infiltrating b cells and their clinical significance in human hepatocellular carcinoma","volume":"8","author":"Zhang","year":"2019","journal-title":"Oncoimmunology"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26731","article-title":"Immunodominance and functional alterations of tumor-associated antigen-specific Cd8+ T-cell responses in hepatocellular carcinoma","volume":"59","author":"Flecken","year":"2014","journal-title":"Hepatology"},{"key":"B70","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1038\/nrgastro.2015.173","article-title":"Immunological landscape and immunotherapy of hepatocellular carcinoma","volume":"12","author":"Prieto","year":"2015","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.Can-06-1278","article-title":"Macrophages regulate the angiogenic switch in a mouse model of breast cancer","volume":"66","author":"Lin","year":"2006","journal-title":"Cancer Res"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.4251\/wjgo.v14.i10.1933","article-title":"Vcan, expressed highly in hepatitis b virus-induced hepatocellular carcinoma, is a potential biomarker for immune checkpoint inhibitors","volume":"14","author":"Wang","year":"2022","journal-title":"World J Gastrointest Oncol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.12659\/msm.930215","article-title":"H long terminal repeat-associating 2 (Hhla2) is a biomarker of advanced stage hepatocellular carcinoma and promotes tumor cell development in vitro","volume":"27","author":"Luo","year":"2021","journal-title":"Med Sci Monit"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.12659\/msm.913094","article-title":"Role of Cd200\/Cd200r signaling pathway in regulation of Cd4+T cell subsets during thermal ablation of hepatocellular carcinoma","volume":"25","author":"Huang","year":"2019","journal-title":"Med Sci Monit"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2016.08.009","article-title":"Cd200r, a Co-inhibitory receptor on immune cells, predicts the prognosis of human hepatocellular carcinoma","volume":"178","author":"Sun","year":"2016","journal-title":"Immunol Lett"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.4149\/neo_2020_200914N982","article-title":"Loss of Neuropilin1 inhibits liver cancer stem cells population and blocks metastasis in hepatocellular carcinoma Via epithelial-mesenchymal transition","volume":"68","author":"Li","year":"2021","journal-title":"Neoplasma"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1080\/2162402x.2016.1234565","article-title":"Impact of myeloid-derived suppressor cell on kupffer cells from mouse livers with hepatocellular carcinoma","volume":"5","author":"Lacotte","year":"2016","journal-title":"Oncoimmunology"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.2147\/ott.S271891","article-title":"Cd276 promotes vasculogenic mimicry formation in hepatocellular carcinoma Via the Pi3k\/Akt\/Mmps pathway","volume":"13","author":"Cheng","year":"2020","journal-title":"Onco Targets Ther"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1177\/1073274820977114","article-title":"Development of a predictive immune-related gene signature associated with hepatocellular carcinoma patient prognosis","volume":"27","author":"Lei","year":"2020","journal-title":"Cancer Control"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1137025\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T04:43:21Z","timestamp":1678855401000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1137025\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,15]]},"references-count":79,"alternative-id":["10.3389\/fimmu.2023.1137025"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1137025","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,15]]},"article-number":"1137025"}}