REFERENCES
1. Rumgay H, Arnold M, Ferlay J, et al. Global burden of primary liver cancer in 2020 and predictions to 2040. J Hepatol. 2022;77:1598-606.
2. Kulik L, El-Serag HB. Epidemiology and management of hepatocellular carcinoma. Gastroenterology. 2019;156:477-91.e1.
3. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209-49.
4. Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021;7:6.
5. Singal AG, Lampertico P, Nahon P. Epidemiology and surveillance for hepatocellular carcinoma: new trends. J Hepatol. 2020;72:250-61.
7. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of hepatocellular carcinoma. J Hepatol. 2018;69:182-236.
8. Xu L, Kim Y, Spolverato G, Gani F, Pawlik TM. Racial disparities in treatment and survival of patients with hepatocellular carcinoma in the United States. Hepatobiliary Surg Nutr. 2016;5:43-52.
9. Altekruse SF, Henley SJ, Cucinelli JE, McGlynn KA. Changing hepatocellular carcinoma incidence and liver cancer mortality rates in the United States. Am J Gastroenterol. 2014;109:542-53.
10. Koza A, Bhogal RH, Fotiadis N, Mavroeidis VK. The role of ablative techniques in the management of hepatocellular carcinoma: indications and outcomes. Biomedicines. 2023;11:1062.
11. Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol. 2022;76:681-93.
12. Llovet JM, De Baere T, Kulik L, et al. Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2021;18:293-313.
13. Llovet JM, Castet F, Heikenwalder M, et al. Immunotherapies for hepatocellular carcinoma. Nat Rev Clin Oncol. 2022;19:151-72.
14. Liu Y, Xun Z, Ma K, et al. Identification of a tumour immune barrier in the HCC microenvironment that determines the efficacy of immunotherapy. J Hepatol. 2023;78:770-82.
15. Galasso L, Cerrito L, Maccauro V, et al. Hepatocellular carcinoma and the multifaceted relationship with its microenvironment: attacking the hepatocellular carcinoma defensive fortress. Cancers. 2024;16:1837.
16. Ladd AD, Duarte S, Sahin I, Zarrinpar A. Mechanisms of drug resistance in HCC. Hepatology. 2024;79:926-40.
17. Hinshaw DC, Shevde LA. The tumor microenvironment innately modulates cancer progression. Cancer Res. 2019;79:4557-66.
18. Chen C, Wang Z, Ding Y, Qin Y. Tumor microenvironment-mediated immune evasion in hepatocellular carcinoma. Front Immunol. 2023;14:1133308.
19. Robinson MW, Harmon C, O’Farrelly C. Liver immunology and its role in inflammation and homeostasis. Cell Mol Immunol. 2016;13:267-76.
20. Hanahan D, Coussens LM. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell. 2012;21:309-22.
21. Volponi C, Gazzillo A, Bonavita E. The tumor microenvironment of hepatocellular carcinoma: untying an intricate immunological network. Cancers. 2022;14:6151.
22. Williams MA, Tyznik AJ, Bevan MJ. Interleukin-2 signals during priming are required for secondary expansion of CD8+ memory T cells. Nature. 2006;441:890-3.
23. Hao X, Sun G, Zhang Y, et al. Targeting immune cells in the tumor microenvironment of HCC: new opportunities and challenges. Front Cell Dev Biol. 2021;9:775462.
24. Wang H, Liu F, Wu X, et al. Cancer-associated fibroblasts contributed to hepatocellular carcinoma recurrence and metastasis via CD36-mediated fatty-acid metabolic reprogramming. Exp Cell Res. 2024;435:113947.
25. Su L, Yue Y, Yan Y, et al. Extracellular vesicles in hepatocellular carcinoma: unraveling immunological mechanisms for enhanced diagnosis and overcoming drug resistance. Front Immunol. 2024;15:1485628.
26. Gupta T, Jarpula NS. Hepatocellular carcinoma immune microenvironment and check point inhibitors-current status. World J Hepatol. 2024;16:353-65.
27. Mignini I, Piccirilli G, Galasso L, et al. From the colon to the liver: how gut microbiota may influence colorectal cancer metastatic potential. J Clin Med. 2024;13:420.
28. Nishida N, Kudo M. Immunological microenvironment of hepatocellular carcinoma and its clinical implication. Oncology. 2017;92 Suppl 1:40-9.
29. Bai Y, Chen D, Cheng C, et al. Immunosuppressive landscape in hepatocellular carcinoma revealed by single-cell sequencing. Front Immunol. 2022;13:950536.
30. Xia C, Chen Y, Zhu Y, et al. Identification of DLAT as a potential therapeutic target via a novel cuproptosis-related gene signature for the prediction of liver cancer prognosis. J Gastrointest Oncol. 2024;15:2230-51.
31. Cariani E, Missale G. Immune landscape of hepatocellular carcinoma microenvironment: implications for prognosis and therapeutic applications. Liver Int. 2019;39:1608-21.
32. Barry KC, Hsu J, Broz ML, et al. A natural killer-dendritic cell axis defines checkpoint therapy-responsive tumor microenvironments. Nat Med. 2018;24:1178-91.
33. Böttcher JP, Bonavita E, Chakravarty P, et al. NK cells stimulate recruitment of cDC1 into the tumor microenvironment promoting cancer immune control. Cell. 2018;172:1022-37.e14.
34. Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39:1-10.
35. Zheng L, Qin S, Si W, et al. Pan-cancer single-cell landscape of tumor-infiltrating T cells. Science. 2021;374:abe6474.
36. Ma L, Hernandez MO, Zhao Y, et al. Tumor cell biodiversity drives microenvironmental reprogramming in liver cancer. Cancer Cell. 2019;36:418-30.e6.
37. Iñarrairaegui M, Melero I, Sangro B. Immunotherapy of hepatocellular carcinoma: facts and hopes. Clin Cancer Res. 2018;24:1518-24.
38. Peng W, Chen JQ, Liu C, et al. Loss of PTEN promotes resistance to T cell-mediated immunotherapy. Cancer Discov. 2016;6:202-16.
39. Lu C, Rong D, Zhang B, et al. Current perspectives on the immunosuppressive tumor microenvironment in hepatocellular carcinoma: challenges and opportunities. Mol Cancer. 2019;18:130.
40. Jaillon S, Ponzetta A, Di Mitri D, Santoni A, Bonecchi R, Mantovani A. Neutrophil diversity and plasticity in tumour progression and therapy. Nat Rev Cancer. 2020;20:485-503.
41. Zhou SL, Zhou ZJ, Hu ZQ, et al. Tumor-associated neutrophils recruit macrophages and T-regulatory cells to promote progression of hepatocellular carcinoma and resistance to sorafenib. Gastroenterology. 2016;150:1646-58.e17.
42. Yang LY, Luo Q, Lu L, et al. Increased neutrophil extracellular traps promote metastasis potential of hepatocellular carcinoma via provoking tumorous inflammatory response. J Hematol Oncol. 2020;13:3.
43. Sun R, Xiong Y, Liu H, et al. Tumor-associated neutrophils suppress antitumor immunity of NK cells through the PD-L1/PD-1 axis. Transl Oncol. 2020;13:100825.
44. Guan X, Lu Y, Zhu H, et al. The crosstalk between cancer cells and neutrophils enhances hepatocellular carcinoma metastasis via neutrophil extracellular traps-associated cathepsin G component: a potential therapeutic target. J Hepatocell Carcinoma. 2021;8:451-65.
45. Li XF, Chen DP, Ouyang FZ, et al. Increased autophagy sustains the survival and pro-tumourigenic effects of neutrophils in human hepatocellular carcinoma. J Hepatol. 2015;62:131-9.
46. Thommen DS, Koelzer VH, Herzig P, et al. A transcriptionally and functionally distinct PD-1+ CD8+ T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade. Nat Med. 2018;24:994-1004.
47. Kunitani H, Shimizu Y, Murata H, Higuchi K, Watanabe A. Phenotypic analysis of circulating and intrahepatic dendritic cell subsets in patients with chronic liver diseases. J Hepatol. 2002;36:734-41.
48. Thaiss CA, Semmling V, Franken L, Wagner H, Kurts C. Chemokines: a new dendritic cell signal for T cell activation. Front Immunol. 2011;2:31.
49. Chen C, Ma YH, Zhang YT, et al. Effect of dendritic cell-based immunotherapy on hepatocellular carcinoma: a systematic review and meta-analysis. Cytotherapy. 2018;20:975-89.
50. Huang Y, Ge W, Zhou J, Gao B, Qian X, Wang W. The role of tumor associated macrophages in hepatocellular carcinoma. J Cancer. 2021;12:1284-94.
51. Dong P, Ma L, Liu L, et al. CD86+/CD206+, diametrically polarized tumor-associated macrophages, predict hepatocellular carcinoma patient prognosis. Int J Mol Sci. 2016;17:320.
52. Zhu Y, Yang J, Xu D, et al. Disruption of tumour-associated macrophage trafficking by the osteopontin-induced colony-stimulating factor-1 signalling sensitises hepatocellular carcinoma to anti-PD-L1 blockade. Gut. 2019;68:1653-66.
53. Zhu XD, Zhang JB, Zhuang PY, et al. High expression of macrophage colony-stimulating factor in peritumoral liver tissue is associated with poor survival after curative resection of hepatocellular carcinoma. J Clin Oncol. 2008;26:2707-16.
54. Veglia F, Sanseviero E, Gabrilovich DI. Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity. Nat Rev Immunol. 2021;21:485-98.
55. Hoechst B, Voigtlaender T, Ormandy L, et al. Myeloid derived suppressor cells inhibit natural killer cells in patients with hepatocellular carcinoma via the NKp30 receptor. Hepatology. 2009;50:799-807.
56. Erez N, Truitt M, Olson P, Arron ST, Hanahan D. Cancer-associated fibroblasts are activated in incipient neoplasia to orchestrate tumor-promoting inflammation in an NF-kappaB-dependent manner. Cancer Cell. 2010;17:135-47.
57. Deng Y, Cheng J, Fu B, et al. Hepatic carcinoma-associated fibroblasts enhance immune suppression by facilitating the generation of myeloid-derived suppressor cells. Oncogene. 2017;36:1090-101.
58. Zhang Q, He Y, Luo N, et al. Landscape and dynamics of single immune cells in hepatocellular carcinoma. Cell. 2019;179:829-45.e20.
59. Guo X, Zhang Y, Zheng L, et al. Global characterization of T cells in non-small-cell lung cancer by single-cell sequencing. Nat Med. 2018;24:978-85.
60. Newell EW, Cheng Y. Mass cytometry: blessed with the curse of dimensionality. Nat Immunol. 2016;17:890-5.
61. Giesen C, Wang HA, Schapiro D, et al. Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry. Nat Methods. 2014;11:417-22.
62. Wan JCM, Massie C, Garcia-Corbacho J, et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat Rev Cancer. 2017;17:223-38.
63. European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma. J Hepatol. 2025;82:315-74.
64. Forner A, Gilabert M, Bruix J, Raoul JL. Treatment of intermediate-stage hepatocellular carcinoma. Nat Rev Clin Oncol. 2014;11:525-35.
65. Ebeling Barbier C, Heindryckx F, Lennernäs H. Limitations and possibilities of transarterial chemotherapeutic treatment of hepatocellular carcinoma. Int J Mol Sci. 2021;22:13051.
66. Liu Z, Tu K, Wang Y, et al. Hypoxia accelerates aggressiveness of hepatocellular carcinoma cells involving oxidative stress, epithelial-mesenchymal transition and non-canonical hedgehog signaling. Cell Physiol Biochem. 2017;44:1856-68.
67. de Baere T, Plotkin S, Yu R, Sutter A, Wu Y, Cruise GM. An in vitro evaluation of four types of drug-eluting microspheres loaded with doxorubicin. J Vasc Interv Radiol. 2016;27:1425-31.
68. Kim MJ, Jang JW, Oh BS, et al. Change in inflammatory cytokine profiles after transarterial chemotherapy in patients with hepatocellular carcinoma. Cytokine. 2013;64:516-22.
70. Katayama K, Imai T, Abe Y, et al. Number of nodules but not size of hepatocellular carcinoma can predict refractoriness to transarterial chemoembolization and poor prognosis. J Clin Med Res. 2018;10:765-71.
71. Kudo M, Matsui O, Izumi N, et al; Liver Cancer Study Group of Japan. Transarterial chemoembolization failure/refractoriness: JSH-LCSGJ criteria 2014 update. Oncology. 2014;87 Suppl 1:22-31.
72. Choi J, Lee D, Shim JH, et al. Evaluation of transarterial chemoembolization refractoriness in patients with hepatocellular carcinoma. PLoS One. 2020;15:e0229696.
73. Tak E, Lee S, Lee J, et al. Human carbonyl reductase 1 upregulated by hypoxia renders resistance to apoptosis in hepatocellular carcinoma cells. J Hepatol. 2011;54:328-39.
74. Singh P, Toom S, Avula A, Kumar V, Rahma OE. The immune modulation effect of locoregional therapies and its potential synergy with immunotherapy in hepatocellular carcinoma. J Hepatocell Carcinoma. 2020;7:11-7.
75. Tampaki M, Ionas E, Hadziyannis E, Deutsch M, Malagari K, Koskinas J. Association of TIM-3 with BCLC stage, serum PD-L1 detection, and response to transarterial chemoembolization in patients with hepatocellular carcinoma. Cancers. 2020;12:212.
76. Jekarl DW, Lee S, Kwon JH, et al. Complex interaction networks of cytokines after transarterial chemotherapy in patients with hepatocellular carcinoma. PLoS One. 2019;14:e0224318.
77. Pinato DJ, Karamanakos G, Arizumi T, et al. Dynamic changes of the inflammation-based index predict mortality following chemoembolisation for hepatocellular carcinoma: a prospective study. Aliment Pharmacol Ther. 2014;40:1270-81.
78. Pinato DJ, Murray SM, Forner A, et al. Trans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma: implications for immunotherapy. J Immunother Cancer. 2021;9:e003311.
79. Tan J, Fan W, Liu T, et al. TREM2+ macrophages suppress CD8+ T-cell infiltration after transarterial chemoembolisation in hepatocellular carcinoma. J Hepatol. 2023;79:126-40.
80. Cappelli A, Cucchetti A, Cabibbo G, et al. Refining prognosis after trans-arterial chemo-embolization for hepatocellular carcinoma. Liver Int. 2016;36:729-36.
81. Kadalayil L, Benini R, Pallan L, et al. A simple prognostic scoring system for patients receiving transarterial embolisation for hepatocellular cancer. Ann Oncol. 2013;24:2565-70.
82. Tang Y, Wu Y, Xue M, Zhu B, Fan W, Li J. A 10-gene signature identified by machine learning for predicting the response to transarterial chemoembolization in patients with hepatocellular carcinoma. J Oncol. 2022;2022:3822773.
83. Fako V, Martin SP, Pomyen Y, et al. Gene signature predictive of hepatocellular carcinoma patient response to transarterial chemoembolization. Int J Biol Sci. 2019;15:2654-63.
84. Huang M, Wang L, Chen J, et al. Regulation of COX-2 expression and epithelial-to-mesenchymal transition by hypoxia-inducible factor-1α is associated with poor prognosis in hepatocellular carcinoma patients post TACE surgery. Int J Oncol. 2016;48:2144-54.
85. He Q, Yang J, Jin Y. Development and validation of TACE refractoriness-related diagnostic and prognostic scores and characterization of tumor microenvironment infiltration in hepatocellular carcinoma. Front Immunol. 2022;13:869993.
86. Wang L, Cao J, Liu Z, et al. Enhanced interactions within microenvironment accelerates dismal prognosis in HBV-related HCC after TACE. Hepatol Commun. 2024;8:e0548.
87. Yue Y, Ren Z, Wang Y, et al. Impact of microparticle transarterial chemoembolization (mTACE) on myeloid-derived suppressor cell subtypes in hepatocellular carcinoma: clinical correlations and therapeutic implications. Immun Inflamm Dis. 2024;12:e70007.
88. Wang C, Leng B, You R, et al. A transcriptomic biomarker for predicting the response to TACE correlates with the tumor microenvironment and radiomics features in hepatocellular carcinoma. J Hepatocell Carcinoma. 2024;11:2321-37.
89. Ayaru L, Pereira SP, Alisa A, et al. Unmasking of alpha-fetoprotein-specific CD4+ T cell responses in hepatocellular carcinoma patients undergoing embolization. J Immunol. 2007;178:1914-22.
90. Xue J, Ni H, Wang F, Xu K, Niu M. Advances in locoregional therapy for hepatocellular carcinoma combined with immunotherapy and targeted therapy. J Interv Med. 2021;4:105-13.
91. El Fouly A, Ertle J, El Dorry A, et al. In intermediate stage hepatocellular carcinoma: radioembolization with yttrium 90 or chemoembolization? Liver Int. 2015;35:627-35.
92. Kallini JR, Gabr A, Salem R, Lewandowski RJ. Transarterial radioembolization with Yttrium-90 for the treatment of hepatocellular carcinoma. Adv Ther. 2016;33:699-714.
93. Salem R, Lewandowski RJ, Mulcahy MF, et al. Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology. 2010;138:52-64.
94. Franzè MS, Vigneron P, Sessa A, et al. Prognostic factors influencing outcomes in hepatocellular carcinoma patients undergoing selective internal radiation therapy. Ann Hepatol. 2025;30:101539.
95. Lugade AA, Sorensen EW, Gerber SA, Moran JP, Frelinger JG, Lord EM. Radiation-induced IFN-gamma production within the tumor microenvironment influences antitumor immunity. J Immunol. 2008;180:3132-9.
96. Barcellos-Hoff MH, Park C, Wright EG. Radiation and the microenvironment - tumorigenesis and therapy. Nat Rev Cancer. 2005;5:867-75.
97. Chew V, Tow C, Teo M, et al. Inflammatory tumour microenvironment is associated with superior survival in hepatocellular carcinoma patients. J Hepatol. 2010;52:370-9.
98. Chew V, Lee YH, Pan L, et al. Immune activation underlies a sustained clinical response to Yttrium-90 radioembolisation in hepatocellular carcinoma. Gut. 2019;68:335-46.
99. Bitar R, Salem R, Finn R, Greten TF, Goldberg SN, Chapiro J. Interventional oncology meets immuno-oncology: combination therapies for hepatocellular carcinoma. Radiology. 2024;313:e232875.
100. Giraud J, Chalopin D, Blanc JF, Saleh M. Hepatocellular carcinoma immune landscape and the potential of immunotherapies. Front Immunol. 2021;12:655697.
101. Farhood B, Najafi M, Mortezaee K. CD8+ cytotoxic T lymphocytes in cancer immunotherapy: a review. J Cell Physiol. 2019;234:8509-21.
102. Wherry EJ, Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol. 2015;15:486-99.
103. Chen L, Huang H, Huang Z, et al. Prognostic values of tissue-resident CD8+T cells in human hepatocellular carcinoma and intrahepatic cholangiocarcinoma. World J Surg Oncol. 2023;21:124.
104. Li Z, Zheng B, Qiu X, et al. The identification and functional analysis of CD8+PD-1+CD161+ T cells in hepatocellular carcinoma. NPJ Precis Oncol. 2020;4:28.
105. Ye L, Li Y, Tang H, et al. CD8+CXCR5+T cells infiltrating hepatocellular carcinomas are activated and predictive of a better prognosis. Aging. 2019;11:8879-91.
106. Abushukair HM, Saeed A. Hepatocellular carcinoma and immunotherapy: beyond immune checkpoint inhibitors. World J Gastrointest Oncol. 2022;14:1210-2.
107. Duan Q, Zhang H, Zheng J, Zhang L. Turning cold into hot: firing up the tumor microenvironment. Trends Cancer. 2020;6:605-18.
108. Ailia MJ, Heo J, Yoo SY. Navigating through the PD-1/PDL-1 landscape: a systematic review and meta-analysis of clinical outcomes in hepatocellular carcinoma and their influence on immunotherapy and tumor microenvironment. Int J Mol Sci. 2023;24:6495.
109. Kudo M. Pembrolizumab for the treatment of hepatocellular carcinoma. Liver Cancer. 2019;8:143-54.
110. Zhu AX, Finn RS, Edeline J, et al; KEYNOTE-224 investigators. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol. 2018;19:940-52.
111. El-Khoueiry AB, Sangro B, Yau T, 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;389:2492-502.
112. Finn RS, Ryoo BY, Merle P, et al; KEYNOTE-240 investigators. Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240: a randomized, double-blind, phase III trial. J Clin Oncol. 2020;38:193-202.
113. Sangro B, Park J, Finn R, et al. LBA-3 CheckMate 459: long-term (minimum follow-up 33.6 months) survival outcomes with nivolumab versus sorafenib as first-line treatment in patients with advanced hepatocellular carcinoma. Ann Oncol. 2020;31:S241-2.
114. Finn RS, Qin S, Ikeda M, et al; IMbrave150 Investigators. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382:1894-905.
115. Salem R, Li D, Sommer N, et al. Characterization of response to atezolizumab+bevacizumab versus sorafenib for hepatocellular carcinoma: results from the IMbrave150 trial. Cancer Med. 2021;10:5437-47.
116. D’Alessio A, Fulgenzi CAM, Nishida N, et al. Preliminary evidence of safety and tolerability of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma and Child-Pugh A and B cirrhosis: a real-world study. Hepatology. 2022;76:1000-12.
117. Sangro B, Gomez-Martin C, de la Mata M, et al. A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C. J Hepatol. 2013;59:81-8.
118. Abou-alfa GK, Chan SL, Kudo M, et al. Phase 3 randomized, open-label, multicenter study of tremelimumab (T) and durvalumab (D) as first-line therapy in patients (pts) with unresectable hepatocellular carcinoma (uHCC): HIMALAYA. J Clin Oncol. 2022;40:379.
119. Yau T, Kang YK, Kim TY, et al. Efficacy and safety of nivolumab plus ipilimumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib: the CheckMate 040 randomized clinical trial. JAMA Oncol. 2020;6:e204564.
120. Zuo D, Zhu Y, Wang K, et al. A novel LAG3 neutralizing antibody improves cancer immunotherapy by dual inhibition of MHC-II and FGL1 ligand binding. Biomed Pharmacother. 2024;175:116782.
121. Yang C, Qian Q, Zhao Y, et al. Fibrinogen-like protein 1 promotes liver-resident memory T-cell exhaustion in hepatocellular carcinoma. Front Immunol. 2023;14:1112672.
122. Hua N, Chen A, Yang C, et al. The correlation of fibrinogen-like protein-1 expression with the progression and prognosis of hepatocellular carcinoma. Mol Biol Rep. 2022;49:7911-9.
123. Guo M, Yuan F, Qi F, et al. Expression and clinical significance of LAG-3, FGL1, PD-L1 and CD8+T cells in hepatocellular carcinoma using multiplex quantitative analysis. J Transl Med. 2020;18:306.
124. Morita M, Nishida N, Aoki T, et al. Role of β-catenin activation in the tumor immune microenvironment and immunotherapy of hepatocellular carcinoma. Cancers. 2023;15:2311.
125. Harding JJ, Nandakumar S, Armenia J, et al. Prospective genotyping of hepatocellular carcinoma: clinical implications of next-generation sequencing for matching patients to targeted and immune therapies. Clin Cancer Res. 2019;25:2116-26.
126. Morita M, Nishida N, Sakai K, et al. Immunological microenvironment predicts the survival of the patients with hepatocellular carcinoma treated with anti-PD-1 antibody. Liver Cancer. 2021;10:380-93.
127. Zhu AX, Abbas AR, de Galarreta MR, et al. Molecular correlates of clinical response and resistance to atezolizumab in combination with bevacizumab in advanced hepatocellular carcinoma. Nat Med. 2022;28:1599-611.
128. Zhang C, Hu S, Yin C, Wang G, Liu P. STAT3 orchestrates immune dynamics in hepatocellular carcinoma: a pivotal nexus in tumor progression. Crit Rev Oncol Hematol. 2025;207:104620.
129. Wang Y, Wang W, Liu K, et al. The mechanism of Xihuang pills’ intervention in the tumour immune microenvironment for the treatment of liver cancer based on the STAT3-PDL1 pathway. J Ethnopharmacol. 2024;331:118278.
130. Blagih J, Buck MD, Vousden KH. p53, cancer and the immune response. J Cell Sci. 2020;133:jcs237453.
131. Wang J, Sanmamed MF, Datar I, et al. Fibrinogen-like protein 1 is a major immune inhibitory ligand of LAG-3. Cell. 2019;176:334-47.e12.
132. Yu R, Zhu B, Chen D. Type I interferon-mediated tumor immunity and its role in immunotherapy. Cell Mol Life Sci. 2022;79:191.
133. Fu Y, Guo X, Sun L, et al. Exploring the role of the immune microenvironment in hepatocellular carcinoma: implications for immunotherapy and drug resistance. Elife. 2024;13:e95009.
134. Kuang DM, Zhao Q, Wu Y, et al. Peritumoral neutrophils link inflammatory response to disease progression by fostering angiogenesis in hepatocellular carcinoma. J Hepatol. 2011;54:948-55.
135. Costa A, Kieffer Y, Scholer-Dahirel A, et al. Fibroblast heterogeneity and immunosuppressive environment in human breast cancer. Cancer Cell. 2018;33:463-79.e10.
136. Mariathasan S, Turley SJ, Nickles D, et al. TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature. 2018;554:544-8.
137. Gudd CLC, Au L, Triantafyllou E, et al. Activation and transcriptional profile of monocytes and CD8+ T cells are altered in checkpoint inhibitor-related hepatitis. J Hepatol. 2021;75:177-89.
138. Pinato DJ, Kaseb A, Wang Y, et al. Impact of corticosteroid therapy on the outcomes of hepatocellular carcinoma treated with immune checkpoint inhibitor therapy. J Immunother Cancer. 2020;8:e000726.
139. Kelley RK, Sangro B, Harris W, 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;39:2991-3001.
140. Cao F, Shi C, Zhang G, Luo J, Zheng J, Hao W. Improved clinical outcomes in advanced hepatocellular carcinoma treated with transarterial chemoembolization plus atezolizumab and bevacizumab: a bicentric retrospective study. BMC Cancer. 2023;23:873.
141. Cui TM, Liu Y, Wang JB, Liu LX. Adverse effects of immune-checkpoint inhibitors in hepatocellular carcinoma. Onco Targets Ther. 2020;13:11725-40.
