{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:00:59Z","timestamp":1790744459796,"version":"4.1.0"},"reference-count":79,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":78,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Shanghai Sailing Program","award":["23YF1433100"],"award-info":[{"award-number":["23YF1433100"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81972229"],"award-info":[{"award-number":["81972229"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Natural Science Foundation of Shanghai","award":["20ZR1473100"],"award-info":[{"award-number":["20ZR1473100"]}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"crossref","award":["2024J011443"],"award-info":[{"award-number":["2024J011443"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Xiamen medical health key project","award":["3502Z20244014"],"award-info":[{"award-number":["3502Z20244014"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Exp Hematol Oncol"],"DOI":"10.1186\/s40164-026-00792-2","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T11:08:26Z","timestamp":1781608106000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Autophagy-promoted immunogenic cell death elicited by tyrosine kinase inhibitor orchestrates a synergistic immunotherapeutic microenvironment in hepatocellular carcinoma"],"prefix":"10.1186","volume":"15","author":[{"given":"Shan-Ru","family":"Feng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"En-Fu","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mo-Ran","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Kwangwari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Qiang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2011Feng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying\u2011Hong","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2011Ren","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2011Xun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan\u2011Ming","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo\u2011Ming","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai\u2011Wu","family":"Ke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-ying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Bo","family":"Qie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu\u2011Tao","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen\u2011Bin","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"issue":"3","key":"792_CR1","first-page":"229","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229\u201363.","journal-title":"CA Cancer J Clin"},{"issue":"1","key":"792_CR2","first-page":"47","volume":"4","author":"B Han","year":"2024","unstructured":"Han B, Zheng R, Zeng H, Wang S, Sun K, Chen R, et al. Cancer incidence and mortality in China, 2022. J Natl Cancer Cent. 2024;4(1):47\u201353.","journal-title":"J Natl Cancer Cent"},{"issue":"9","key":"792_CR3","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/j.hlife.2024.06.007","volume":"2","author":"Z-B Ding","year":"2024","unstructured":"Ding Z-B, Shi Y-H, Chen J-F, Fan J, Zhou J. Recent advances in surgical management strategies for hepatocellular carcinoma. hLife. 2024;2(9):439\u201353.","journal-title":"hLife"},{"issue":"5","key":"792_CR4","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1016\/j.annonc.2025.02.006","volume":"36","author":"A Vogel","year":"2025","unstructured":"Vogel A, Chan SL, Dawson LA, Kelley RK, Llovet JM, Meyer T, et al. Hepatocellular carcinoma: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2025;36(5):491\u2013506.","journal-title":"Ann Oncol"},{"issue":"10","key":"792_CR5","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1038\/s41571-018-0073-4","volume":"15","author":"JM Llovet","year":"2018","unstructured":"Llovet JM, Montal R, Sia D, Finn RS. Molecular therapies and precision medicine for hepatocellular carcinoma. Nat Rev Clin Oncol. 2018;15(10):599\u2013616.","journal-title":"Nat Rev Clin Oncol"},{"issue":"5","key":"792_CR6","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41575-020-00395-0","volume":"18","author":"JM Llovet","year":"2021","unstructured":"Llovet JM, De Baere T, Kulik L, Haber PK, Greten TF, Meyer T, et al. Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2021;18(5):293\u2013313.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"2","key":"792_CR7","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/S1470-2045(18)30937-9","volume":"20","author":"AX Zhu","year":"2019","unstructured":"Zhu AX, Kang YK, Yen CJ, Finn RS, Galle PR, Llovet JM, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased \u03b1-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(2):282\u201396.","journal-title":"Lancet Oncol"},{"issue":"6","key":"792_CR8","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1016\/S1470-2045(20)30156-X","volume":"21","author":"MS Lee","year":"2020","unstructured":"Lee MS, Ryoo BY, Hsu CH, Numata K, Stein S, Verret W, et al. Atezolizumab with or without bevacizumab in unresectable hepatocellular carcinoma (GO30140): an open-label, multicentre, phase 1b study. Lancet Oncol. 2020;21(6):808\u201320.","journal-title":"Lancet Oncol"},{"issue":"10088","key":"792_CR9","doi-asserted-by":"publisher","first-page":"2492","DOI":"10.1016\/S0140-6736(17)31046-2","volume":"389","author":"AB El-Khoueiry","year":"2017","unstructured":"El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1\/2 dose escalation and expansion trial. Lancet. 2017;389(10088):2492\u2013502.","journal-title":"Lancet"},{"issue":"26","key":"792_CR10","doi-asserted-by":"publisher","first-page":"2960","DOI":"10.1200\/JCO.20.00808","volume":"38","author":"RS Finn","year":"2020","unstructured":"Finn RS, Ikeda M, Zhu AX, Sung MW, Baron AD, Kudo M, et al. Phase Ib study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma. J Clin Oncol. 2020;38(26):2960\u201370.","journal-title":"J Clin Oncol"},{"issue":"20","key":"792_CR11","doi-asserted-by":"publisher","first-page":"1894","DOI":"10.1056\/NEJMoa1915745","volume":"382","author":"RS Finn","year":"2020","unstructured":"Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382(20):1894\u2013905.","journal-title":"N Engl J Med"},{"key":"792_CR12","doi-asserted-by":"publisher","first-page":"viii718","DOI":"10.1093\/annonc\/mdy424.028","volume":"29","author":"MJ Pishvaian","year":"2018","unstructured":"Pishvaian MJ, Lee MS, Ryoo BY, Stein S, Lee KH, Verret W, et al. Updated safety and clinical activity results from a phase Ib study of atezolizumab + bevacizumab in hepatocellular carcinoma (HCC). Ann Oncol. 2018;29:viii718\u20139.","journal-title":"Ann Oncol"},{"issue":"11","key":"792_CR13","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202105631","volume":"9","author":"Y Wang","year":"2022","unstructured":"Wang Y, Zhao Q, Zhao B, Zheng Y, Zhuang Q, Liao N, et al. Remodeling tumor-associated neutrophils to enhance dendritic cell-based HCC neoantigen nano-vaccine efficiency. Adv Sci (Weinh). 2022;9(11):e2105631.","journal-title":"Adv Sci (Weinh)"},{"issue":"2","key":"792_CR14","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. Diagnosis and management of toxicities of immune checkpoint inhibitors in hepatocellular carcinoma. J Hepatol. 2020;72(2):320\u201341.","journal-title":"J Hepatol"},{"issue":"27","key":"792_CR15","doi-asserted-by":"publisher","first-page":"2991","DOI":"10.1200\/JCO.20.03555","volume":"39","author":"RK Kelley","year":"2021","unstructured":"Kelley RK, Sangro B, Harris W, Ikeda M, Okusaka T, Kang YK, et al. Safety, efficacy, and pharmacodynamics of tremelimumab plus durvalumab for patients with unresectable hepatocellular carcinoma: randomized expansion of a phase I\/II study. J Clin Oncol. 2021;39(27):2991\u20133001.","journal-title":"J Clin Oncol"},{"issue":"1","key":"792_CR16","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1002\/hep.31479","volume":"73","author":"GS Feng","year":"2021","unstructured":"Feng GS, Hanley KL, Liang Y, Lin X. Improving the efficacy of liver cancer immunotherapy: the power of combined preclinical and clinical studies. Hepatology. 2021;73(1):104\u201314.","journal-title":"Hepatology"},{"issue":"1","key":"792_CR17","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1186\/s13045-025-01739-6","volume":"18","author":"S Dai","year":"2025","unstructured":"Dai S, Chen Y, Cai W, Dong S, Zhao J, Chen L, et al. Combination immunotherapy in hepatocellular carcinoma: synergies among immune checkpoints, TKIs, and chemotherapy. J Hematol Oncol. 2025;18(1):85.","journal-title":"J Hematol Oncol"},{"issue":"1","key":"792_CR18","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1186\/s13045-024-01647-1","volume":"17","author":"Y Chen","year":"2024","unstructured":"Chen Y, Dai S, Cheng CS, Chen L. Lenvatinib and immune-checkpoint inhibitors in hepatocellular carcinoma: mechanistic insights, clinical efficacy, and future perspectives. J Hematol Oncol. 2024;17(1):130.","journal-title":"J Hematol Oncol"},{"issue":"1","key":"792_CR19","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s40164-025-00636-5","volume":"14","author":"J Tong","year":"2025","unstructured":"Tong J, Tan Y, Ouyang W, Chang H. Targeting immune checkpoints in hepatocellular carcinoma therapy: toward combination strategies with curative potential. Exp Hematol Oncol. 2025;14(1):65.","journal-title":"Exp Hematol Oncol"},{"issue":"6","key":"792_CR20","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1038\/s41573-024-00920-9","volume":"23","author":"L Galluzzi","year":"2024","unstructured":"Galluzzi L, Guilbaud E, Schmidt D, Kroemer G, Marincola FM. Targeting immunogenic cell stress and death for cancer therapy. Nat Rev Drug Discov. 2024;23(6):445\u201360.","journal-title":"Nat Rev Drug Discov"},{"key":"792_CR21","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.968686","volume":"13","author":"S Wang","year":"2022","unstructured":"Wang S, Wang G, Wu W, Xu Z, Yang J, Cao M, et al. Autophagy activation by dietary piceatannol enhances the efficacy of immunogenic chemotherapy. Front Immunol. 2022;13:968686.","journal-title":"Front Immunol"},{"issue":"4","key":"792_CR22","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1038\/s41590-022-01132-2","volume":"23","author":"G Kroemer","year":"2022","unstructured":"Kroemer G, Galassi C, Zitvogel L, Galluzzi L. Immunogenic cell stress and death. Nat Immunol. 2022;23(4):487\u2013500.","journal-title":"Nat Immunol"},{"issue":"12","key":"792_CR23","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1038\/s41571-020-0413-z","volume":"17","author":"L Galluzzi","year":"2020","unstructured":"Galluzzi L, Humeau J, Buqu\u00e9 A, Zitvogel L, Kroemer G. Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors. Nat Rev Clin Oncol. 2020;17(12):725\u201341.","journal-title":"Nat Rev Clin Oncol"},{"issue":"6062","key":"792_CR24","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1126\/science.1208347","volume":"334","author":"M Michaud","year":"6062","unstructured":"Michaud M, Martins I, Sukkurwala AQ, Adjemian S, Ma Y, Pellegatti P, et al. Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice. Science. 6062;334(6062):1573\u20137.","journal-title":"Science"},{"issue":"8","key":"792_CR25","doi-asserted-by":"publisher","first-page":"2087","DOI":"10.1038\/s41591-023-02497-z","volume":"29","author":"M Thibaudin","year":"2023","unstructured":"Thibaudin M, Fumet JD, Chibaudel B, Bennouna J, Borg C, Martin-Babau J, et al. First-line durvalumab and tremelimumab with chemotherapy in RAS-mutated metastatic colorectal cancer: a phase 1b\/2 trial. Nat Med. 2023;29(8):2087\u201398.","journal-title":"Nat Med"},{"issue":"6","key":"792_CR26","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1038\/s41591-019-0432-4","volume":"25","author":"L Voorwerk","year":"2019","unstructured":"Voorwerk L, Slagter M, Horlings HM, Sikorska K, van de Vijver KK, de Maaker M, et al. Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial. Nat Med. 2019;25(6):920\u20138.","journal-title":"Nat Med"},{"issue":"1","key":"792_CR27","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1158\/2159-8290.CD-NB2015-158","volume":"6","author":"A Poh","year":"2016","unstructured":"Poh A. First oncolytic viral therapy for melanoma. Cancer Discov. 2016;6(1):6.","journal-title":"Cancer Discov"},{"issue":"8","key":"792_CR28","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1038\/s41577-018-0014-6","volume":"18","author":"PK Bommareddy","year":"2018","unstructured":"Bommareddy PK, Shettigar M, Kaufman HL. Integrating oncolytic viruses in combination cancer immunotherapy. Nat Rev Immunol. 2018;18(8):498\u2013513.","journal-title":"Nat Rev Immunol"},{"issue":"3","key":"792_CR29","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1038\/s41571-022-00719-w","volume":"20","author":"SZ Shalhout","year":"2023","unstructured":"Shalhout SZ, Miller DM, Emerick KS, Kaufman HL. Therapy with oncolytic viruses: progress and challenges. Nat Rev Clin Oncol. 2023;20(3):160\u201377.","journal-title":"Nat Rev Clin Oncol"},{"issue":"6","key":"792_CR30","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1053\/j.seminoncol.2016.10.005","volume":"43","author":"C Grigg","year":"2016","unstructured":"Grigg C, Blake Z, Gartrell R, Sacher A, Taback B, Saenger Y. Talimogene laherparepvec (T-Vec) for the treatment of melanoma and other cancers. Semin Oncol. 2016;43(6):638\u201346.","journal-title":"Semin Oncol"},{"issue":"3","key":"792_CR31","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1073\/pnas.94.3.843","volume":"94","author":"B He","year":"1997","unstructured":"He B, Gross M, Roizman B. The gamma(1)34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1alpha to dephosphorylate the alpha subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase. Proc Natl Acad Sci U S A. 1997;94(3):843\u20138.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"792_CR32","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s12943-018-0801-5","volume":"17","author":"Q Jiao","year":"2018","unstructured":"Jiao Q, Bi L, Ren Y, Song S, Wang Q, Wang YS. Advances in studies of tyrosine kinase inhibitors and their acquired resistance. Mol Cancer. 2018;17(1):36.","journal-title":"Mol Cancer"},{"key":"792_CR33","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.755433","volume":"11","author":"F Scirocchi","year":"2021","unstructured":"Scirocchi F, Napoletano C, Pace A, Rahimi Koshkaki H, Di Filippo A, Zizzari IG, et al. Immunogenic cell death and immunomodulatory effects of cabozantinib. Front Oncol. 2021;11:755433.","journal-title":"Front Oncol"},{"issue":"1","key":"792_CR34","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1038\/s41467-019-09415-3","volume":"10","author":"P Liu","year":"2019","unstructured":"Liu P, Zhao L, Pol J, Levesque S, Petrazzuolo A, Pfirschke C, et al. Crizotinib-induced immunogenic cell death in non-small cell lung cancer. Nat Commun. 2019;10(1):1486.","journal-title":"Nat Commun"},{"issue":"1","key":"792_CR35","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1038\/nm1523","volume":"13","author":"M Obeid","year":"2007","unstructured":"Obeid M, Tesniere A, Ghiringhelli F, Fimia GM, Apetoh L, Perfettini JL, et al. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med. 2007;13(1):54\u201361.","journal-title":"Nat Med"},{"issue":"11","key":"792_CR36","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1038\/s41419-020-03221-2","volume":"11","author":"J Fucikova","year":"2020","unstructured":"Fucikova J, Kepp O, Kasikova L, Petroni G, Yamazaki T, Liu P, et al. Detection of immunogenic cell death and its relevance for cancer therapy. Cell Death Dis. 2020;11(11):1013.","journal-title":"Cell Death Dis"},{"issue":"4","key":"792_CR37","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1111\/cas.13536","volume":"109","author":"C Xie","year":"2018","unstructured":"Xie C, Wan X, Quan H, Zheng M, Fu L, Li Y, et al. Preclinical characterization of anlotinib, a highly potent and selective vascular endothelial growth factor receptor-2 inhibitor. Cancer Sci. 2018;109(4):1207\u201319.","journal-title":"Cancer Sci"},{"issue":"10","key":"792_CR38","doi-asserted-by":"publisher","first-page":"3344","DOI":"10.1002\/cam4.2941","volume":"9","author":"ZM Wang","year":"2020","unstructured":"Wang ZM, Zhang SL, Yang H, Zhuang RY, Guo X, Tong HX, et al. Efficacy and safety of anlotinib, a multikinase angiogenesis inhibitor, in combination with epirubicin in preclinical models of soft tissue sarcoma. Cancer Med. 2020;9(10):3344\u201352.","journal-title":"Cancer Med"},{"issue":"1","key":"792_CR39","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1186\/s12957-025-03810-5","volume":"23","author":"S Zhao","year":"2025","unstructured":"Zhao S, Meng M, Cheng R, Zhang M, Liu C, Meng Q, et al. Anlotinib inhibits c-MET and ITGA2 in the treatment of anaplastic thyroid carcinoma. World J Surg Oncol. 2025;23(1):161.","journal-title":"World J Surg Oncol"},{"issue":"4","key":"792_CR40","doi-asserted-by":"publisher","first-page":"729","DOI":"10.3390\/cancers13040729","volume":"13","author":"AM Monjazeb","year":"2021","unstructured":"Monjazeb AM, Wang Z, Vick LV, Dunai C, Minnar C, Khuat LT, et al. Mouse preclinical cancer immunotherapy modeling involving anti-PD-1 therapies reveals the need to use mouse reagents to mirror clinical paradigms. Cancers [Internet]. 2021;13(4):729.","journal-title":"Cancers [Internet]"},{"issue":"4","key":"792_CR41","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1158\/1078-0432.CCR-18-2407","volume":"25","author":"BM Larimer","year":"2019","unstructured":"Larimer BM, Bloch E, Nesti S, Austin EE, Wehrenberg-Klee E, Boland G, et al. The effectiveness of checkpoint inhibitor combinations and administration timing can be measured by granzyme B PET imaging. Clin Cancer Res. 2019;25(4):1196\u2013205.","journal-title":"Clin Cancer Res"},{"key":"792_CR42","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13040729","author":"AM Monjazeb","year":"2021","unstructured":"Monjazeb AM, Wang Z, Vick LV, Dunai C, Minnar C, Khuat LT, et al. Mouse preclinical cancer immunotherapy modeling involving anti-PD-1 therapies reveals the need to use mouse reagents to mirror clinical paradigms. Cancers (Basel). 2021. https:\/\/doi.org\/10.3390\/cancers13040729.","journal-title":"Cancers (Basel)"},{"issue":"8","key":"792_CR43","doi-asserted-by":"publisher","first-page":"3029","DOI":"10.1073\/pnas.0712394105","volume":"105","author":"ML Lin","year":"2008","unstructured":"Lin ML, Zhan Y, Proietto AI, Prato S, Wu L, Heath WR, et al. Selective suicide of cross-presenting CD8+ dendritic cells by cytochrome c injection shows functional heterogeneity within this subset. Proc Natl Acad Sci U S A. 2008;105(8):3029\u201334.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"792_CR44","doi-asserted-by":"publisher","first-page":"4127","DOI":"10.4049\/jimmunol.0803364","volume":"182","author":"C-H Qiu","year":"2009","unstructured":"Qiu C-H, Miyake Y, Kaise H, Kitamura H, Ohara O, Tanaka M. Novel subset of CD8\u03b1+ dendritic cells localized in the marginal zone is responsible for tolerance to cell-associated Antigens1. J Immunol. 2009;182(7):4127\u201336.","journal-title":"J Immunol"},{"issue":"8","key":"792_CR45","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.it.2013.02.007","volume":"34","author":"S Nierkens","year":"2013","unstructured":"Nierkens S, Tel J, Janssen E, Adema GJ. Antigen cross-presentation by dendritic cell subsets: one general or all sergeants? Trends Immunol. 2013;34(8):361\u201370.","journal-title":"Trends Immunol"},{"issue":"2","key":"792_CR46","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1016\/j.cell.2019.08.052","volume":"179","author":"Q Gao","year":"2019","unstructured":"Gao Q, Zhu H, Dong L, Shi W, Chen R, Song Z, et al. Integrated proteogenomic characterization of HBV-related hepatocellular carcinoma. Cell. 2019;179(2):561-77.e22.","journal-title":"Cell"},{"key":"792_CR47","doi-asserted-by":"publisher","DOI":"10.3390\/biom14010108","author":"X Liu","year":"2024","unstructured":"Liu X, Yao S, Feng Y, Li P, Li Y, Xia S. Construction of a novel damage-associated molecular-pattern-related signature to assess lung adenocarcinoma\u2019s prognosis and immune landscape. Biomolecules. 2024. https:\/\/doi.org\/10.3390\/biom14010108.","journal-title":"Biomolecules"},{"issue":"4","key":"792_CR48","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.70678","volume":"14","author":"L Li","year":"2025","unstructured":"Li L, Yang Y, Peng M, Wang B, Zhu L, Chen C, et al. Molecular subtyping and therapeutic targeting of IFNG-driven immunogenic cell death in lung adenocarcinoma. Cancer Med. 2025;14(4):e70678.","journal-title":"Cancer Med"},{"issue":"16","key":"792_CR49","doi-asserted-by":"publisher","first-page":"7683","DOI":"10.1093\/nar\/gkt563","volume":"41","author":"W B'Chir","year":"2013","unstructured":"B\u2019Chir W, Maurin AC, Carraro V, Averous J, Jousse C, Muranishi Y, et al. The eIF2\u03b1\/ATF4 pathway is essential for stress-induced autophagy gene expression. Nucleic Acids Res. 2013;41(16):7683\u201399.","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"792_CR50","doi-asserted-by":"publisher","first-page":"3500","DOI":"10.1038\/s41467-021-23864-9","volume":"12","author":"M Wu","year":"2021","unstructured":"Wu M, Xia X, Hu J, Fowlkes NW, Li S. WSX1 act as a tumor suppressor in hepatocellular carcinoma by downregulating neoplastic PD-L1 expression. Nat Commun. 2021;12(1):3500.","journal-title":"Nat Commun"},{"key":"792_CR51","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.semcancer.2020.07.001","volume":"79","author":"O Melaiu","year":"2022","unstructured":"Melaiu O, Lucarini V, Giovannoni R, Fruci D, Gemignani F. News on immune checkpoint inhibitors as immunotherapy strategies in adult and pediatric solid tumors. Semin Cancer Biol. 2022;79:18\u201343.","journal-title":"Semin Cancer Biol"},{"issue":"2","key":"792_CR52","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202203973","volume":"10","author":"B Tang","year":"2023","unstructured":"Tang B, Zhu J, Wang Y, Chen W, Fang S, Mao W, et al. Targeted xCT-mediated ferroptosis and protumoral polarization of macrophages is effective against HCC and enhances the efficacy of the anti-PD-1\/L1 response. Adv Sci (Weinh). 2023;10(2):e2203973.","journal-title":"Adv Sci (Weinh)"},{"key":"792_CR53","doi-asserted-by":"publisher","first-page":"1070961","DOI":"10.3389\/fimmu.2022.1070961","volume":"13","author":"Q Li","year":"2022","unstructured":"Li Q, Han J, Yang Y, Chen Y. PD-1\/PD-L1 checkpoint inhibitors in advanced hepatocellular carcinoma immunotherapy. Front Immunol. 2022;13:1070961.","journal-title":"Front Immunol"},{"key":"792_CR54","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/j.jconrel.2024.02.036","volume":"368","author":"L Yin","year":"2024","unstructured":"Yin L, Wei Y, Liu Y, Mo X, Song J, Cai W. Bio-responsive Au-miR-183 inhibitor enhances immunotherapy in hepatocellular carcinoma by inducing immunogenic cell death. J Control Release. 2024;368:498\u2013517.","journal-title":"J Control Release"},{"key":"792_CR55","doi-asserted-by":"publisher","first-page":"29","DOI":"10.21037\/tgh-23-11","volume":"8","author":"K Sankar","year":"2023","unstructured":"Sankar K, Pearson AN, Worlikar T, Perricone MD, Holcomb EA, Mendiratta-Lala M, et al. Impact of immune tolerance mechanisms on the efficacy of immunotherapy in primary and secondary liver cancers. Transl Gastroenterol Hepatol. 2023;8:29.","journal-title":"Transl Gastroenterol Hepatol"},{"issue":"1","key":"792_CR56","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s40164-024-00539-x","volume":"13","author":"Y Yin","year":"2024","unstructured":"Yin Y, Feng W, Chen J, Chen X, Wang G, Wang S, et al. Immunosuppressive tumor microenvironment in the progression, metastasis, and therapy of hepatocellular carcinoma: from bench to bedside. Exp Hematol Oncol. 2024;13(1):72.","journal-title":"Exp Hematol Oncol"},{"issue":"1","key":"792_CR57","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s40164-024-00543-1","volume":"13","author":"S Zheng","year":"2024","unstructured":"Zheng S, Wang W, Shen L, Yao Y, Xia W, Ni C. Tumor battlefield within inflamed, excluded or desert immune phenotypes: the mechanisms and strategies. Exp Hematol Oncol. 2024;13(1):80.","journal-title":"Exp Hematol Oncol"},{"issue":"3","key":"792_CR58","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/j.jhep.2021.11.018","volume":"76","author":"M Reig","year":"2022","unstructured":"Reig M, Forner A, Rimola J, Ferrer-F\u00e0brega J, Burrel M, Garcia-Criado \u00c1, et al. BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol. 2022;76(3):681\u201393.","journal-title":"J Hepatol"},{"issue":"2","key":"792_CR59","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/j.jhep.2025.03.017","volume":"83","author":"European Association for the Study of the Liver","year":"2025","unstructured":"European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of autoimmune hepatitis. J Hepatol. 2025;83(2):453\u2013501.","journal-title":"J Hepatol"},{"issue":"1","key":"792_CR60","doi-asserted-by":"publisher","first-page":"19","DOI":"10.17998\/jlc.2025.02.03","volume":"25","author":"H Shin","year":"2025","unstructured":"Shin H, Yu SJ. A concise review of updated global guidelines for the management of hepatocellular carcinoma: 2017\u20132024. J Liver Cancer. 2025;25(1):19\u201330.","journal-title":"J Liver Cancer"},{"issue":"10126","key":"792_CR61","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. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391(10126):1163\u201373.","journal-title":"Lancet"},{"issue":"1","key":"792_CR62","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2020.188391","volume":"1874","author":"Y Zhao","year":"2020","unstructured":"Zhao Y, Zhang YN, Wang KT, Chen L. Lenvatinib for hepatocellular carcinoma: from preclinical mechanisms to anti-cancer therapy. Biochim Biophys Acta Rev Cancer. 2020;1874(1):188391.","journal-title":"Biochim Biophys Acta Rev Cancer"},{"key":"792_CR63","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.728018","volume":"11","author":"KP Fabian","year":"2021","unstructured":"Fabian KP, Wolfson B, Hodge JW. From immunogenic cell death to immunogenic modulation: select chemotherapy regimens induce a spectrum of immune-enhancing activities in the tumor microenvironment. Front Oncol. 2021;11:728018.","journal-title":"Front Oncol"},{"issue":"1","key":"792_CR64","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2019-000337","volume":"8","author":"L Galluzzi","year":"2020","unstructured":"Galluzzi L, Vitale I, Warren S, Adjemian S, Agostinis P, Martinez AB, et al. Consensus guidelines for the definition, detection and interpretation of immunogenic cell death. J Immunother Cancer. 2020;8(1):e000337.","journal-title":"J Immunother Cancer"},{"issue":"4","key":"792_CR65","doi-asserted-by":"publisher","first-page":"4265","DOI":"10.1021\/acsami.9b19148","volume":"12","author":"X Deng","year":"2020","unstructured":"Deng X, Guan W, Qing X, Yang W, Que Y, Tan L, et al. Ultrafast low-temperature photothermal therapy activates autophagy and recovers immunity for efficient antitumor treatment. ACS Appl Mater Interfaces. 2020;12(4):4265\u201375.","journal-title":"ACS Appl Mater Interfaces"},{"issue":"47","key":"792_CR66","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202412730","volume":"36","author":"Y Xing","year":"2024","unstructured":"Xing Y, Yang J, Peng A, Qian Y, Liu Y, Pan P, et al. Lysosome targeted nanoparticle aggregation reverses immunosuppressive tumor microenvironment for cancer immunotherapy. Adv Mater. 2024;36(47):e2412730.","journal-title":"Adv Mater"},{"issue":"9","key":"792_CR67","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.4161\/auto.25399","volume":"9","author":"AD Garg","year":"2013","unstructured":"Garg AD, Dudek AM, Ferreira GB, Verfaillie T, Vandenabeele P, Krysko DV, et al. ROS-induced autophagy in cancer cells assists in evasion from determinants of immunogenic cell death. Autophagy. 2013;9(9):1292\u2013307.","journal-title":"Autophagy"},{"issue":"3","key":"792_CR68","doi-asserted-by":"publisher","first-page":"46","DOI":"10.4291\/wjgp.v14.i3.46","volume":"14","author":"HB Choudhary","year":"2023","unstructured":"Choudhary HB, Mandlik SK, Mandlik DS. Role of p53 suppression in the pathogenesis of hepatocellular carcinoma. World J Gastrointest Pathophysiol. 2023;14(3):46\u201370.","journal-title":"World J Gastrointest Pathophysiol"},{"issue":"1","key":"792_CR69","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1038\/s41392-024-01992-0","volume":"9","author":"H Duan","year":"2024","unstructured":"Duan H, Shao C, Luo Z, Wang T, Tong L, Liu H, et al. Perioperative sintilimab and neoadjuvant anlotinib plus chemotherapy for resectable non-small-cell lung cancer: a multicentre, open-label, single-arm, phase 2 trial (TD-NeoFOUR trial). Signal Transduct Target Ther. 2024;9(1):296.","journal-title":"Signal Transduct Target Ther"},{"issue":"15","key":"792_CR70","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1056\/NEJMoa0806470","volume":"359","author":"RR Holman","year":"2008","unstructured":"Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359(15):1577\u201389.","journal-title":"N Engl J Med"},{"issue":"9","key":"792_CR71","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1007\/s00125-017-4349-5","volume":"60","author":"WM Valencia","year":"2017","unstructured":"Valencia WM, Palacio A, Tamariz L, Florez H. Metformin and ageing: improving ageing outcomes beyond glycaemic control. Diabetologia. 2017;60(9):1630\u20138.","journal-title":"Diabetologia"},{"issue":"5","key":"792_CR72","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1038\/nri2546","volume":"9","author":"AW Thomson","year":"2009","unstructured":"Thomson AW, Turnquist HR, Raimondi G. Immunoregulatory functions of mTOR inhibition. Nat Rev Immunol. 2009;9(5):324\u201337.","journal-title":"Nat Rev Immunol"},{"issue":"10","key":"792_CR73","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1038\/nri3901","volume":"15","author":"T Weichhart","year":"2015","unstructured":"Weichhart T, Hengstschl\u00e4ger M, Linke M. Regulation of innate immune cell function by mTOR. Nat Rev Immunol. 2015;15(10):599\u2013614.","journal-title":"Nat Rev Immunol"},{"issue":"6","key":"792_CR74","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1073\/pnas.1417636112","volume":"112","author":"S Eikawa","year":"2015","unstructured":"Eikawa S, Nishida M, Mizukami S, Yamazaki C, Nakayama E, Udono H. Immune-mediated antitumor effect by type 2 diabetes drug, metformin. Proc Natl Acad Sci U S A. 2015;112(6):1809\u201314.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"792_CR75","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.596655","volume":"8","author":"HY Lai","year":"2020","unstructured":"Lai HY, Tsai HH, Yen CJ, Hung LY, Yang CC, Ho CH, et al. Metformin resensitizes sorafenib-resistant HCC cells through AMPK-dependent autophagy activation. Front Cell Dev Biol. 2020;8:596655.","journal-title":"Front Cell Dev Biol"},{"issue":"6","key":"792_CR76","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1016\/S1470-2045(25)00190-1","volume":"26","author":"J Zhou","year":"2025","unstructured":"Zhou J, Bai L, Luo J, Bai Y, Pan Y, Yang X, et al. Anlotinib plus penpulimab versus sorafenib in the first-line treatment of unresectable hepatocellular carcinoma (APOLLO): a randomised, controlled, phase 3 trial. Lancet Oncol. 2025;26(6):719\u201331.","journal-title":"Lancet Oncol"},{"key":"792_CR77","doi-asserted-by":"publisher","first-page":"5479491","DOI":"10.1155\/2022\/5479491","volume":"2022","author":"M Yuan","year":"2022","unstructured":"Yuan M, Zhai Y, Men Y, Zhao M, Sun X, Ma Z, et al. Anlotinib enhances the antitumor activity of high-dose irradiation combined with Anti-PD-L1 by potentiating the tumor immune microenvironment in murine lung cancer. Oxid Med Cell Longev. 2022;2022:5479491.","journal-title":"Oxid Med Cell Longev"},{"issue":"1","key":"792_CR78","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1186\/s40164-025-00705-9","volume":"14","author":"Y Wang","year":"2025","unstructured":"Wang Y, Jiang C, Zhou H, Han R. Transforming cancer immunotherapy: integration of distinct immune-based approaches as redefined dual immunotherapy with potential third-sensitizer. Exp Hematol Oncol. 2025;14(1):114.","journal-title":"Exp Hematol Oncol"},{"issue":"1","key":"792_CR79","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s13045-024-01549-2","volume":"17","author":"KY Shen","year":"2024","unstructured":"Shen KY, Zhu Y, Xie SZ, Qin LX. Immunosuppressive tumor microenvironment and immunotherapy of hepatocellular carcinoma: current status and prospectives. J Hematol Oncol. 2024;17(1):25.","journal-title":"J Hematol Oncol"}],"container-title":["Experimental Hematology & Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40164-026-00792-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40164-026-00792-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40164-026-00792-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T14:03:17Z","timestamp":1788357797000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s40164-026-00792-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,16]]},"references-count":79,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["792"],"URL":"https:\/\/doi.org\/10.1186\/s40164-026-00792-2","relation":{},"ISSN":["2162-3619"],"issn-type":[{"value":"2162-3619","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,16]]},"assertion":[{"value":"23 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Ethical approval was provided by the Ethics Committee of Zhongshan Hospital, and written informed consent was obtained from each patient.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"85"}}