{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:00:09Z","timestamp":1790143209465,"version":"4.0.1"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":81,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100019155","name":"Nanjing Drum Tower Hospital","doi-asserted-by":"publisher","award":["No. 2024-LCYJ-PY-59"],"award-info":[{"award-number":["No. 2024-LCYJ-PY-59"]}],"id":[{"id":"10.13039\/501100019155","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The National Health Commission Health Development Research Center","award":["No. WKZX2023CX020001"],"award-info":[{"award-number":["No. WKZX2023CX020001"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Immunol Immunother"],"DOI":"10.1007\/s00262-026-04485-x","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T12:06:12Z","timestamp":1783080372000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multidimensional analysis of tumour immune microenvironment in HCC: prognostic significance and implications for immunotherapy"],"prefix":"10.1007","volume":"75","author":[{"given":"Jun","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzhen","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyan","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xintao","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Pu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojiao","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sihui","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuting","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"issue":"3","key":"4485_CR1","first-page":"229","volume":"74","author":"F Bray","year":"2022","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I et al (2022) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 74(3):229\u2013263","journal-title":"CA Cancer J Clin"},{"issue":"4","key":"4485_CR2","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1056\/NEJMoa0708857","volume":"359","author":"JM Llovet","year":"2008","unstructured":"Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359(4):378\u2013390","journal-title":"N Engl J Med"},{"issue":"10126","key":"4485_CR3","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1016\/S0140-6736(18)30207-1","volume":"391","author":"M Kudo","year":"2018","unstructured":"Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F et al (2018) Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet 391(10126):1163\u20131173","journal-title":"Lancet"},{"key":"4485_CR4","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.788635","volume":"11","author":"S Zhu","year":"2021","unstructured":"Zhu S, Liu C, Dong Y, Shao J, Liu B, Shen J (2021) A retrospective study of Lenvatinib monotherapy or combined with programmed cell death protein 1 antibody in the treatment of patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma in China. Front Oncol 11:788635","journal-title":"Front Oncol"},{"issue":"2","key":"4485_CR5","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.jhep.2019.10.021","volume":"72","author":"B Sangro","year":"2020","unstructured":"Sangro B, Chan SL, Meyer T, Reig M, El-Khoueiry A, Galle PR (2020) Diagnosis and management of toxicities of immune checkpoint inhibitors in hepatocellular carcinoma. J Hepatol 72(2):320\u2013341","journal-title":"J Hepatol"},{"issue":"2","key":"4485_CR6","first-page":"141","volume":"53","author":"EC Paver","year":"2021","unstructured":"Paver EC, Cooper WA, Colebatch AJ, Ferguson PM, Hill SK, Lum T et al (2021) Programmed death ligand-1 (PD-L1) as a predictive marker for immunotherapy in solid tumours: a guide to immunohistochemistry implementation and interpretation. Pathology (Phila) 53(2):141\u2013156","journal-title":"Pathology (Phila)"},{"issue":"1","key":"4485_CR7","doi-asserted-by":"publisher","first-page":"11738","DOI":"10.1038\/s41598-018-30277-0","volume":"8","author":"J Kim","year":"2018","unstructured":"Kim J, Cho J, Lee MH, Lim JH (2018) Relative efficacy of checkpoint inhibitors for advanced NSCLC according to programmed death-ligand-1 expression: a systematic review and network meta-analysis. Sci Rep 8(1):11738","journal-title":"Sci Rep"},{"issue":"11","key":"4485_CR8","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1038\/s41571-023-00816-4","volume":"20","author":"TF Greten","year":"2023","unstructured":"Greten TF, Villanueva A, Korangy F, Ruf B, Yarchoan M, Ma L et al (2023) Biomarkers for immunotherapy of hepatocellular carcinoma. Nat Rev Clin Oncol 20(11):780\u2013798","journal-title":"Nat Rev Clin Oncol"},{"issue":"25","key":"4485_CR9","doi-asserted-by":"publisher","first-page":"2500","DOI":"10.1056\/NEJMc1713444","volume":"377","author":"M Yarchoan","year":"2017","unstructured":"Yarchoan M, Hopkins A, Jaffee EM (2017) Tumour mutational burden and response rate to PD-1 inhibition. N Engl J Med 377(25):2500\u20132501","journal-title":"N Engl J Med"},{"issue":"8","key":"4485_CR10","doi-asserted-by":"publisher","first-page":"1599","DOI":"10.1038\/s41591-022-01868-2","volume":"28","author":"AX Zhu","year":"2022","unstructured":"Zhu AX, Abbas AR, de Galarreta MR, Guan Y, Lu S, Koeppen H et al (2022) Molecular correlates of clinical response and resistance to atezolizumab in combination with bevacizumab in advanced hepatocellular carcinoma. Nat Med 28(8):1599\u20131611","journal-title":"Nat Med"},{"issue":"6","key":"4485_CR11","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1016\/j.jhep.2020.07.026","volume":"73","author":"B Sangro","year":"2020","unstructured":"Sangro B, Melero I, Wadhawan S, Finn RS, Abou-Alfa GK, Cheng AL et al (2020) Association of inflammatory biomarkers with clinical outcomes in nivolumab-treated patients with advanced hepatocellular carcinoma. J Hepatol 73(6):1460\u20131469","journal-title":"J Hepatol"},{"issue":"2","key":"4485_CR12","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-000987","volume":"8","author":"HHM Ng","year":"2020","unstructured":"Ng HHM, Lee RY, Goh S, Tay ISY, Lim X, Lee B et al (2020) Immunohistochemical scoring of CD38 in the tumour microenvironment predicts responsiveness to anti-PD-1\/PD-L1 immunotherapy in hepatocellular carcinoma. J Immunother Cancer 8(2):e000987","journal-title":"J Immunother Cancer"},{"issue":"18","key":"4485_CR13","doi-asserted-by":"publisher","first-page":"2586","DOI":"10.1200\/JCO.2006.09.4565","volume":"25","author":"Q Gao","year":"2007","unstructured":"Gao Q, Qiu SJ, Fan J, Zhou J, Wang XY, Xiao YS et al (2007) Intratumoural balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection. J Clin Oncol 25(18):2586\u20132593","journal-title":"J Clin Oncol"},{"issue":"3","key":"4485_CR14","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1158\/1078-0432.CCR-06-2363","volume":"13","author":"N Kobayashi","year":"2007","unstructured":"Kobayashi N, Hiraoka N, Yamagami W, Ojima H, Kanai Y, Kosuge T et al (2007) FOXP3+ regulatory T cells affect the development and progression of hepatocarcinogenesis. Clin Cancer Res 13(3):902\u2013911","journal-title":"Clin Cancer Res"},{"issue":"5","key":"4485_CR15","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1016\/j.jhep.2008.12.033","volume":"50","author":"JP Zhang","year":"2009","unstructured":"Zhang JP, Yan J, Xu J, Pang XH, Chen MS, Li L et al (2009) Increased intratumoural IL-17-producing cells correlate with poor survival in hepatocellular carcinoma patients. J Hepatol 50(5):980\u2013989","journal-title":"J Hepatol"},{"issue":"6","key":"4485_CR16","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1046\/j.1365-2559.2000.00952.x","volume":"37","author":"JF Emile","year":"2000","unstructured":"Emile JF, Adam R, Sebagh M, Marchadier E, Falissard B, Dussaix E et al (2000) Hepatocellular carcinoma with lymphoid stroma: a tumour with good prognosis after liver transplantation. Histopathology 37(6):523\u2013529","journal-title":"Histopathology"},{"issue":"7","key":"4485_CR17","doi-asserted-by":"publisher","first-page":"1438","DOI":"10.1016\/j.ajpath.2017.02.022","volume":"187","author":"I Labgaa","year":"2017","unstructured":"Labgaa I, Stueck A, Ward SC (2017) Lymphoepithelioma-like carcinoma in liver. Am J Pathol 187(7):1438\u20131444","journal-title":"Am J Pathol"},{"key":"4485_CR18","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/s41586-022-05400-x","volume":"612","author":"R Xue","year":"2022","unstructured":"Xue R, Zhang Q, Cao Q, Kong R, Xiang X, Liu H et al (2022) Liver tumour immune microenvironment subtypes and neutrophil heterogeneity. Nature 612:141\u2013147","journal-title":"Nature"},{"issue":"3","key":"4485_CR19","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1016\/j.jhep.2019.09.032","volume":"72","author":"YC Shen","year":"2020","unstructured":"Shen YC, Hsu CL, Jeng YM, Ho MC, Ho CM, Yeh CP et al (2020) Reliability of a single-region sample to evaluate tumor immune microenvironment in hepatocellular carcinoma. J Hepatol 72(3):489\u2013497","journal-title":"J Hepatol"},{"key":"4485_CR20","doi-asserted-by":"publisher","first-page":"4851","DOI":"10.1038\/s41467-022-32570-z","volume":"13","author":"Y Chen","year":"2022","unstructured":"Chen Y, Jia K, Sun Y, Zhang C, Li Y, Zhang L et al (2022) Predicting response to immunotherapy in gastric cancer via multi-dimensional analyses of the tumour immune microenvironment. Nat Commun 13:4851","journal-title":"Nat Commun"},{"key":"4485_CR21","doi-asserted-by":"publisher","first-page":"2482","DOI":"10.1038\/s41588-025-02351-7","volume":"57","author":"TN Aung","year":"2025","unstructured":"Aung TN, Monkman J, Warrell J, Vathiotis L, Bates KM, Gavrielatou N et al (2025) Spatial signatures for predicting immunotherapy outcomes using multi-omics in non-small cell lung cancer. Nat Genet 57:2482\u20132493","journal-title":"Nat Genet"},{"issue":"1","key":"4485_CR22","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/s41698-018-0048-z","volume":"2","author":"LX Yu","year":"2018","unstructured":"Yu LX, Ling Y, Wang HY (2018) Role of nonresolving inflammation in hepatocellular carcinoma development and progression. NPJ Precis Oncol 2(1):6","journal-title":"NPJ Precis Oncol"},{"issue":"4","key":"4485_CR23","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1053\/j.gastro.2017.06.017","volume":"153","author":"G Zhou","year":"2017","unstructured":"Zhou G, Sprengers D, Boor PPC, Doukas M, Schutz H, Mancham S et al (2017) Antibodies against immune checkpoint molecules restore functions of tumor-infiltrating T cells in hepatocellular carcinomas. Gastroenterology 153(4):1107-1119.e10","journal-title":"Gastroenterology"},{"issue":"8","key":"4485_CR24","doi-asserted-by":"publisher","first-page":"2682","DOI":"10.1007\/s00259-022-05723-x","volume":"49","author":"S An","year":"2022","unstructured":"An S, Zhang D, Zhang Y, Wang C, Shi L, Wei W et al (2022) GPC3-targeted immunoPET imaging of hepatocellular carcinomas. Eur J Nucl Med Mol Imaging 49(8):2682\u20132692","journal-title":"Eur J Nucl Med Mol Imaging"},{"issue":"10","key":"4485_CR25","doi-asserted-by":"publisher","first-page":"2056","DOI":"10.1158\/0008-5472.CAN-19-1629","volume":"80","author":"S Wang","year":"2020","unstructured":"Wang S, Rong R, Yang DM, Fujimoto J, Yan S, Cai L et al (2020) Computational staining of pathology images to study the tumor microenvironment in lung cancer. Cancer Res 80(10):2056\u20132066","journal-title":"Cancer Res"},{"issue":"12","key":"4485_CR26","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1002\/cac2.12383","volume":"42","author":"F Wu","year":"2022","unstructured":"Wu F, Jiang T, Chen G, Huang Y, Zhou J, Lin L et al (2022) Multiplexed imaging of tumor immune microenvironmental markers in locally advanced or metastatic non-small-cell lung cancer characterizes the features of response to PD-1 blockade plus chemotherapy. Cancer Commun 42(12):1331\u20131346","journal-title":"Cancer Commun"},{"issue":"6","key":"4485_CR27","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1038\/s41591-023-02345-0","volume":"29","author":"A Magen","year":"2023","unstructured":"Magen A, Hamon P, Fiaschi N, Soong BY, Park MD, Mattiuz R et al (2023) Intratumoral dendritic cell-CD4+ T helper cell niches enable CD8+ T cell differentiation following PD-1 blockade in hepatocellular carcinoma. Nat Med 29(6):1389\u20131399","journal-title":"Nat Med"},{"issue":"8","key":"4485_CR28","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.1038\/s41416-023-02183-4","volume":"128","author":"Q Zhou","year":"2023","unstructured":"Zhou Q, Ou Y, Dai X, Chen X, Wu S, Chen W et al (2023) Prevalence of tumour-infiltrating CD103+ cells identifies therapeutic-sensitive prostate cancer with poor clinical outcome. Br J Cancer 128(8):1466\u20131477","journal-title":"Br J Cancer"},{"issue":"12","key":"4485_CR29","doi-asserted-by":"publisher","first-page":"2082","DOI":"10.1016\/j.ccell.2024.10.012","volume":"42","author":"CX Huang","year":"2024","unstructured":"Huang CX, Lao XM, Wang XY, Ren YZ, Lu YT, Shi W et al (2024) Pericancerous cross-presentation to cytotoxic T lymphocytes impairs immunotherapeutic efficacy in hepatocellular carcinoma. Cancer Cell 42(12):2082-2097.e10","journal-title":"Cancer Cell"},{"issue":"7","key":"4485_CR30","doi-asserted-by":"publisher","first-page":"3475","DOI":"10.4049\/jimmunol.1402711","volume":"194","author":"F Djenidi","year":"2015","unstructured":"Djenidi F, Adam J, Goubar A, Durgeau A, Meurice G, de Montpr\u00e9ville V et al (2015) CD8+CD103+ tumor-infiltrating lymphocytes are tumor-specific tissue-resident memory T cells and a prognostic factor for survival in lung cancer patients. J Immunol 194(7):3475\u20133486","journal-title":"J Immunol"},{"issue":"2","key":"4485_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.103785","volume":"25","author":"Y Zheng","year":"2022","unstructured":"Zheng Y, Han L, Chen Z, Li Y, Zhou B, Hu R et al (2022) PD-L1+CD8+ T cells enrichment in lung cancer exerted regulatory function and tumor-promoting tolerance. iScience 25(2):103785","journal-title":"iScience"},{"key":"4485_CR32","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/s41577-025-01211-z","volume":"26","author":"AU Kabir","year":"2026","unstructured":"Kabir AU, Subramanian M, Kwon Y, Choi K (2026) Linking tumour angiogenesis and tumour immunity. Nat Rev Immunol 26:35\u201351","journal-title":"Nat Rev Immunol"},{"issue":"1","key":"4485_CR33","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.jhep.2024.02.009","volume":"81","author":"P Xie","year":"2024","unstructured":"Xie P, Yu M, Zhang B, Yu Q, Zhao Y, Wu M et al (2024) CRKL dictates anti-PD-1 resistance by mediating tumour-associated neutrophil infiltration in hepatocellular carcinoma. J Hepatol 81(1):93\u2013107","journal-title":"J Hepatol"}],"container-title":["Cancer Immunology, Immunotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00262-026-04485-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00262-026-04485-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00262-026-04485-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:01:55Z","timestamp":1790139715000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00262-026-04485-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,3]]},"references-count":33,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["4485"],"URL":"https:\/\/doi.org\/10.1007\/s00262-026-04485-x","relation":{},"ISSN":["1432-0851"],"issn-type":[{"value":"1432-0851","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,3]]},"assertion":[{"value":"13 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study had adhered to the principles stated in the 'Declaration of Helsinki'. This study protocol was reviewed and approved by ethics committee of Drum Tower Hospital of Nanjing University. The patients\/participants provided their written informed consent to participate in this study.","order":2,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"230"}}