REFERENCES
1. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74:229-63.
2. Han B, Zheng R, Zeng H, et al. Cancer incidence and mortality in China, 2022. J Natl Cancer Cent. 2024;4:47-53.
3. Rimassa L, Finn RS, Sangro B. Combination immunotherapy for hepatocellular carcinoma. J Hepatol. 2023;79:506-15.
4. Zheng J, Shao M, Yang W, Ren J, Chen X, Yang H. Benefits of combination therapy with immune checkpoint inhibitors and predictive role of tumour mutation burden in hepatocellular carcinoma: a systematic review and meta-analysis. Int Immunopharmacol. 2022;112:109244.
5. Llovet JM, Castet F, Heikenwalder M, et al. Immunotherapies for hepatocellular carcinoma. Nat Rev Clin Oncol. 2022;19:151-72.
6. Zheng J, Wang S, Xia L, et al. Hepatocellular carcinoma: signaling pathways and therapeutic advances. Signal Transduct Target Ther. 2025;10:35.
7. 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.
8. Wang H, Liang Y, Liu Z, et al. POSTN+ cancer-associated fibroblasts determine the efficacy of immunotherapy in hepatocellular carcinoma. J Immunother Cancer. 2024;12:e008721.
9. Yang C, Geng H, Yang X, et al. Targeting the immune privilege of tumor-initiating cells to enhance cancer immunotherapy. Cancer Cell. 2024;42:2064-81.e19.
10. Xiao Y, Yu D. Tumor microenvironment as a therapeutic target in cancer. Pharmacol Ther. 2021;221:107753.
11. Bejarano L, Jordāo MJC, Joyce JA. Therapeutic targeting of the tumor microenvironment. Cancer Discov. 2021;11:933-59.
12. Gottwick C, Carambia A, Herkel J. Harnessing the liver to induce antigen-specific immune tolerance. Semin Immunopathol. 2022;44:475-84.
13. Henriques-Pons A, Vacani-Martins N, Dos Santos CLP, Meuser-Batista M. The liver’s dilemma: sensing real danger in a sea of PAMPs: the (arterial) sinusoidal segment theory. Front Immunol. 2024;15:1503063.
14. Thomson AW, Knolle PA. Antigen-presenting cell function in the tolerogenic liver environment. Nat Rev Immunol. 2010;10:753-66.
17. Balogh J, Victor D 3rd, Asham EH, et al. Hepatocellular carcinoma: a review. J Hepatocell Carcinoma. 2016;3:41-53.
18. Baumert TF, Jühling F, Ono A, Hoshida Y. Hepatitis C-related hepatocellular carcinoma in the era of new generation antivirals. BMC Med. 2017;15:52.
19. Kudo M. Changing the treatment paradigm for hepatocellular carcinoma using atezolizumab plus bevacizumab combination therapy. Cancers. 2021;13:5475.
20. Jiang X, Wang J, Deng X, et al. Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape. Mol Cancer. 2019;18:10.
21. Noy R, Pollard JW. Tumor-associated macrophages: from mechanisms to therapy. Immunity. 2014;41:49-61.
22. Wang D, Yang L, Yue D, et al. Macrophage-derived CCL22 promotes an immunosuppressive tumor microenvironment via IL-8 in malignant pleural effusion. Cancer Lett. 2019;452:244-53.
23. Yang CL, Song R, Hu JW, et al. Integrating single-cell and bulk RNA sequencing reveals CK19 + cancer stem cells and their specific SPP1 + tumor-associated macrophage niche in HBV-related hepatocellular carcinoma. Hepatol Int. 2024;18:73-90.
24. Chen S, Zhang P, Zhu G, et al. Targeting GSDME-mediated macrophage polarization for enhanced antitumor immunity in hepatocellular carcinoma. Cell Mol Immunol. 2024;21:1505-21.
25. Li L, Sun P, Zhang C, Li Z, Cui K, Zhou W. MiR-98 modulates macrophage polarization and suppresses the effects of tumor-associated macrophages on promoting invasion and epithelial-mesenchymal transition of hepatocellular carcinoma. Cancer Cell Int. 2018;18:95.
26. Lu Y, Sun Q, Guan Q, et al. The XOR-IDH3α axis controls macrophage polarization in hepatocellular carcinoma. J Hepatol. 2023;79:1172-84.
27. Jiang Y, Han Q, Zhao H, Zhang J. Promotion of epithelial-mesenchymal transformation by hepatocellular carcinoma-educated macrophages through Wnt2b/β-catenin/c-Myc signaling and reprogramming glycolysis. J Exp Clin Cancer Res. 2021;40:13.
28. Gao Z, Li XG, Feng SR, et al. Autophagy suppression facilitates macrophage M2 polarization via increased instability of NF-κB pathway in hepatocellular carcinoma. Int Immunopharmacol. 2023;123:110685.
29. Lu CS, Shiau AL, Su BH, et al. Oct4 promotes M2 macrophage polarization through upregulation of macrophage colony-stimulating factor in lung cancer. J Hematol Oncol. 2020;13:62.
30. Wei CY, Zhu MX, Zhang PF, et al. PKCα/ZFP64/CSF1 axis resets the tumor microenvironment and fuels anti-PD1 resistance in hepatocellular carcinoma. J Hepatol. 2022;77:163-76.
31. Feng R, Cui Z, Yang L, Liu Z. Sphingosine 1-phosphate derived from tumor-educated hepatic stellate cells combining with S1PR4 promotes tumor associated macrophages differentiation through FAO modulation. Sci Rep. 2025;15:20507.
32. Kim DH, Kang YN, Jin J, et al. Glutamine-derived aspartate is required for eIF5A hypusination-mediated translation of HIF-1α to induce the polarization of tumor-associated macrophages. Exp Mol Med. 2024;56:1123-36.
33. Zhang X, Lao M, Sun K, et al. Sphingolipid synthesis in tumor-associated macrophages confers immunotherapy resistance in hepatocellular carcinoma. Sci Adv. 2025;11:eadv0558.
34. Yang X, Deng B, Zhao W, et al. FABP5+ lipid-loaded macrophages process tumour-derived unsaturated fatty acid signal to suppress T-cell antitumour immunity. J Hepatol. 2025;82:676-89.
35. Cai J, Zhang P, Cai Y, et al. Lactylation-driven NUPR1 promotes immunosuppression of tumor-infiltrating macrophages in hepatocellular carcinoma. Adv Sci. 2025;12:e2413095.
36. Yu H, Pan J, Zheng S, et al. Hepatocellular carcinoma cell-derived exosomal miR-21-5p induces macrophage M2 polarization by targeting RhoB. Int J Mol Sci. 2023;24:4593.
37. Li X, Yao W, Yuan Y, et al. Targeting of tumour-infiltrating macrophages via CCL2/CCR2 signalling as a therapeutic strategy against hepatocellular carcinoma. Gut. 2017;66:157-67.
38. Chen J, Feng W, Sun M, et al. TGF-β1-induced SOX18 elevation promotes hepatocellular carcinoma progression and metastasis through transcriptionally upregulating PD-L1 and CXCL12. Gastroenterology. 2024;167:264-80.
39. Piqué-Gili M, Andreu-Oller C, Mesropian A, et al. Oncogenic role of PMEPA1 and its association with immune exhaustion and TGF-β activation in HCC. JHEP Rep. 2024;6:101212.
40. Xie M, Lin Z, Ji X, et al. FGF19/FGFR4-mediated elevation of ETV4 facilitates hepatocellular carcinoma metastasis by upregulating PD-L1 and CCL2. J Hepatol. 2023;79:109-25.
41. Wang D, Li X, Li J, et al. APOBEC3B interaction with PRC2 modulates microenvironment to promote HCC progression. Gut. 2019;68:1846-57.
42. Nosaka T, Ohtani M, Yamashita J, et al. PD-L1+ tumor-associated macrophages induce CD8+ T Cell exhaustion in hepatocellular carcinoma. Neoplasia. 2025;69:101234.
43. Liu Z, Wang Y, Dou C, et al. Hypoxia-induced up-regulation of VASP promotes invasiveness and metastasis of hepatocellular carcinoma. Theranostics. 2018;8:4649-63.
44. Wei X, Wang H, Liu H, et al. Disruption of tumor-intrinsic PGAM5 increases anti-PD-1 efficacy through the CCL2 signaling pathway. J Immunother Cancer. 2025;13:e009993.
45. Zhang W, Liu Y, Yan Z, et al. IL-6 promotes PD-L1 expression in monocytes and macrophages by decreasing protein tyrosine phosphatase receptor type O expression in human hepatocellular carcinoma. J Immunother Cancer. 2020;8:e000285.
46. Sun Y, Zhou P, Qian J, et al. Spermine synthase engages in macrophages M2 polarization to sabotage antitumor immunity in hepatocellular carcinoma. Cell Death Differ. 2025;32:573-86.
47. 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.
48. Ceredig R, Rolink AG, Brown G. Models of haematopoiesis: seeing the wood for the trees. Nat Rev Immunol. 2009;9:293-300.
49. Goldmann O, Medina E. Metabolic pathways fueling the suppressive activity of myeloid-derived suppressor cells. Front Immunol. 2024;15:1461455.
50. Alicea-Torres K, Sanseviero E, Gui J, et al. Immune suppressive activity of myeloid-derived suppressor cells in cancer requires inactivation of the type I interferon pathway. Nat Commun. 2021;12:1717.
51. Bronte V, Brandau S, Chen SH, et al. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat Commun. 2016;7:12150.
53. Törnell A, Blick E, Al-Dury S, et al. Presence of MDSC associates with impaired antigen-specific T cell reactivity following COVID-19 vaccination in cirrhotic patients. Front Immunol. 2023;14:1287287.
54. Chivite-Lacaba M, Justo I, Utrero-Rico A, et al. Delineation of monocytic and early-stage myeloid-derived suppressor cells in the peripheral blood of patients with hepatocarcinoma. Int J Cancer. 2025;156:2416-28.
55. Santagata S, Rea G, Castaldo D, et al. Hepatocellular carcinoma (HCC) tumor microenvironment is more suppressive than colorectal cancer liver metastasis (CRLM) tumor microenvironment. Hepatol Int. 2024;18:568-81.
56. Wu X, Pan B, Chu C, et al. CXCL16/CXCR6/TGF-β feedback loop between M-MDSCs and Treg inhibits anti-bacterial immunity during biofilm infection. Adv Sci. 2025;12:e2409537.
57. Noman MZ, Desantis G, Janji B, et al. PD-L1 is a novel direct target of HIF-1α, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J Exp Med. 2014;211:781-90.
58. Zhang Z, Huang W, Hu D, et al. E-twenty-six-specific sequence variant 5 (ETV5) facilitates hepatocellular carcinoma progression and metastasis through enhancing polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC)-mediated immunosuppression. Gut. 2025;74:1137-49.
59. Xia S, Wu J, Zhou W, et al. SLC7A2 deficiency promotes hepatocellular carcinoma progression by enhancing recruitment of myeloid-derived suppressors cells. Cell Death Dis. 2021;12:570.
60. Hoechst B, Ormandy LA, Ballmaier M, et al. A new population of myeloid-derived suppressor cells in hepatocellular carcinoma patients induces CD4+CD25+Foxp3+ T cells. Gastroenterology. 2008;135:234-43.
61. Yashaswini CN, Qin T, Bhattacharya D, et al. Phenotypes and ontogeny of senescent hepatic stellate cells in metabolic dysfunction-associated steatohepatitis. J Hepatol. 2024;81:207-17.
62. Gavin MA, Rasmussen JP, Fontenot JD, et al. Foxp3-dependent programme of regulatory T-cell differentiation. Nature. 2007;445:771-5.
63. Tan SN, Hao J, Ge J, et al. Regulatory T cells converted from Th1 cells in tumors suppress cancer immunity via CD39. J Exp Med. 2025;222:e20240445.
64. Moreau JM, Velegraki M, Bolyard C, Rosenblum MD, Li Z. Transforming growth factor-β1 in regulatory T cell biology. Sci Immunol. 2022;7:eabi4613.
65. Shiri AM, Fard-Aghaie M, Bedke T, et al. Foxp3 + Treg-derived IL-10 promotes colorectal cancer-derived lung metastasis. Sci Rep. 2024;14:30483.
66. Sawant DV, Yano H, Chikina M, et al. Adaptive plasticity of IL-10+ and IL-35+ Treg cells cooperatively promotes tumor T cell exhaustion. Nat Immunol. 2019;20:724-35.
67. Tekguc M, Wing JB, Osaki M, Long J, Sakaguchi S. Treg-expressed CTLA-4 depletes CD80/CD86 by trogocytosis, releasing free PD-L1 on antigen-presenting cells. Proc Natl Acad Sci U S A. 2021;118:e2023739118.
68. Huang CT, Workman CJ, Flies D, et al. Role of LAG-3 in regulatory T cells. Immunity. 2004;21:503-13.
69. Pan B, Yao Y, Wu H, et al. N-glycosylated LTβR increases the Th17/Treg cell ratio in liver cancer by blocking RORC ubiquitination and FOXP3 transcription. Cell Death Dis. 2025;16:421.
70. Li Q, Zhang L, You W, et al. PRDM1/BLIMP1 induces cancer immune evasion by modulating the USP22-SPI1-PD-L1 axis in hepatocellular carcinoma cells. Nat Commun. 2022;13:7677.
71. Gao Y, You M, Fu J, et al. Intratumoral stem-like CCR4+ regulatory T cells orchestrate the immunosuppressive microenvironment in HCC associated with hepatitis B. J Hepatol. 2022;76:148-59.
72. Li S, Xia H, Wang Z, et al. Intratumoral microbial heterogeneity affected tumor immune microenvironment and determined clinical outcome of HBV-related HCC. Hepatology. 2023;78:1079-91.
73. Ding J, Liu H, Zhang X, et al. Integrative multiomic analysis identifies distinct molecular subtypes of NAFLD in a Chinese population. Sci Transl Med. 2024;16:eadh9940.
74. Nong Y, Chen X, Zhang B, et al. M2 macrophages and tumor cells engage in a metabolic feedback loop to drive HCC progression. Sci Rep. 2025;15:41701.
75. Qin SK, Li Q, Ming Xu J, et al. Icaritin-induced immunomodulatory efficacy in advanced hepatitis B virus-related hepatocellular carcinoma: immunodynamic biomarkers and overall survival. Cancer Sci. 2020;111:4218-31.
76. Kalathil S, Lugade AA, Miller A, Iyer R, Thanavala Y. Higher frequencies of GARP+CTLA-4+Foxp3+ T regulatory cells and myeloid-derived suppressor cells in hepatocellular carcinoma patients are associated with impaired T-cell functionality. Cancer Res. 2013;73:2435-44.
77. Li A, Ji B, Yang Y, et al. Single-cell RNA sequencing highlights the role of PVR/PVRL2 in the immunosuppressive tumour microenvironment in hepatocellular carcinoma. Front Immunol. 2023;14:1164448.
78. Wen J, Zhang X, Wong CC, et al. Targeting squalene epoxidase restores anti-PD-1 efficacy in metabolic dysfunction-associated steatohepatitis-induced hepatocellular carcinoma. Gut. 2024;73:2023-36.
79. Gu X, Wei H, Suo C, et al. Itaconate promotes hepatocellular carcinoma progression by epigenetic induction of CD8+ T-cell exhaustion. Nat Commun. 2023;14:8154.
80. Huang J, Tsang WY, Fang XN, et al. FASN inhibition decreases MHC-I degradation and synergizes with PD-L1 checkpoint blockade in hepatocellular carcinoma. Cancer Res. 2024;84:855-71.
81. Barends M, Koller N, Schölz C, et al. Dynamic interactome of the MHC I peptide loading complex in human dendritic cells. Proc Natl Acad Sci U S A. 2023;120:e2219790120.
82. Zhang CY, Liu S, Yang M. Nutrition deprivation affects the cytotoxic effect of CD8 T cells in hepatocellular carcinoma. World J Gastrointest Oncol. 2022;14:1887-91.
83. Bai X, Zhou Y, Yokota Y, et al. Adaptive antitumor immune response stimulated by bio-nanoparticle based vaccine and checkpoint blockade. J Exp Clin Cancer Res. 2022;41:132.
84. Eberhardt CS, Kissick HT, Patel MR, et al. Functional HPV-specific PD-1+ stem-like CD8 T cells in head and neck cancer. Nature. 2021;597:279-84.
85. Huang H, Pan Y, Mai Q, et al. Targeting CDCP1 boost CD8+ T cells-mediated cytotoxicity in cervical cancer via the JAK/STAT signaling pathway. J Immunother Cancer. 2024;12:e009416.
86. Zhao L, Yuan H, Wang Y, et al. p-STAT3-elevated E3 ubiquitin ligase DTX4 confers the stability of HBV cccDNA by ubiquitinating APOBEC3B in liver. Theranostics. 2024;14:6036-52.
87. De Simone V, Franzè E, Ronchetti G, et al. Th17-type cytokines, IL-6 and TNF-α synergistically activate STAT3 and NF-kB to promote colorectal cancer cell growth. Oncogene. 2015;34:3493-503.
88. Wang T, Fan Y, Tan S, et al. Probiotics and their metabolite spermidine enhance IFN-γ+CD4+ T cell immunity to inhibit hepatitis B virus. Cell Rep Med. 2024;5:101822.
89. Mohammadi-Kordkhayli M, Sahraian MA, Ghorbani S, et al. Vitamins A and D enhance the expression of Ror-γ-targeting miRNAs in a mouse model of multiple sclerosis. Mol Neurobiol. 2023;60:5853-65.
90. Gharibi T, Barpour N, Hosseini A, et al. STA-21, a small molecule STAT3 inhibitor, ameliorates experimental autoimmune encephalomyelitis by altering Th-17/Treg balance. Int Immunopharmacol. 2023;119:110160.
91. Motavalli R, Soltani-Zangbar MS, Fereydoonzadeh K, et al. Evaluation of T helper17 as skeletal homeostasis factor in peripheral blood mononuclear cells and T helper cells of end-stage renal disease cases with impaired parathyroid hormone. Mol Biol Rep. 2023;50:4097-104.
92. Wang H, Herman A, Barrow F, et al. Single-cell RNA sequencing reveals a reprogramming of hepatic immune cells and a protective role for B cells in MASH-driven HCC. Hepatol Commun. 2025;9:e0668.
93. Cinnamon E, Stein I, Zino E, et al. RORc-expressing immune cells negatively regulate tertiary lymphoid structure formation and support their pro-tumorigenic functions. J Hepatol. 2025;82:1050-67.
94. Morsing AE, Green K, Clausen S, et al. Age-associated B cells enhance tertiary lymphoid structures in the liver and promote HCC formation. Hepatol Commun. 2025;9:e0816.
95. Lian SL, Lu YT, Lu YJ, Yao YL, Wang XL, Jiang RQ. Tumor-associated macrophages promoting PD-L1 expression in infiltrating B cells through the CXCL12/CXCR4 axis in human hepatocellular carcinoma. Am J Cancer Res. 2024;14:832-53.
96. Zhang B, Vogelzang A, Miyajima M, et al. B cell-derived GABA elicits IL-10+ macrophages to limit anti-tumour immunity. Nature. 2021;599:471-6.
97. Chen Z, Zhang G, Ren X, et al. Cross-talk between myeloid and B cells shapes the distinct microenvironments of primary and secondary liver cancer. Cancer Res. 2023;83:3544-61.
98. Zou J, Luo C, Xin H, et al. The role of tumor-infiltrating B cells in the tumor microenvironment of hepatocellular carcinoma and its prognostic value: a bioinformatics analysis. J Gastrointest Oncol. 2022;13:1959-66.
99. Schaafsma E, Jiang C, Cheng C. B cell infiltration is highly associated with prognosis and an immune-infiltrated tumor microenvironment in neuroblastoma. J Cancer Metastasis Treat. 2021;7:34.
100. Tavakoli S, Samareh-Salavati M, Abdolahi S, et al. Cell therapy using anti-NKG2A pretreated natural killer cells in patients with hepatocellular carcinoma. Adv Pharm Bull. 2024;14:918-26.
101. Yu L, Liu X, Wang X, et al. TIGIT+ TIM-3+ NK cells are correlated with NK cell exhaustion and disease progression in patients with hepatitis B virus‑related hepatocellular carcinoma. Oncoimmunology. 2021;10:1942673.
102. Xi F, Sun H, Peng H, et al. Hepatocyte-derived FGL1 accelerates liver metastasis and tumor growth by inhibiting CD8+ T and NK cells. JCI Insight. 2024;9:e173215.
103. Cheng X, Tan X, Wang W, et al. Long-Chain acylcarnitines induce senescence of invariant natural killer T cells in hepatocellular carcinoma. Cancer Res. 2023;83:582-94.
104. Han J, Ke C, Jiang B, Zhou H, Xu H, Xie X. Down-regulation of PR/SET domain 10 underlies natural killer cell dysfunction in hepatocellular carcinoma. Clin Exp Immunol. 2021;206:366-77.
105. Cui C, Fu K, Yang L, et al. Hypoxia-inducible gene 2 promotes the immune escape of hepatocellular carcinoma from nature killer cells through the interleukin-10-STAT3 signaling pathway. J Exp Clin Cancer Res. 2019;38:229.
106. Shin SK, Oh S, Chun SK, et al. Immune signature and therapeutic approach of natural killer cell in chronic liver disease and hepatocellular carcinoma. J Gastroenterol Hepatol. 2024;39:1717-27.
107. MacNabb BW, Chen X, Tumuluru S, et al. Dendritic cells can prime anti-tumor CD8+ T cell responses through major histocompatibility complex cross-dressing. Immunity. 2022;55:2206-8.
108. Li T, Li B, Lin L, et al. Anti-CTLA-4 antibody self-presented dendritic cell nanovesicles boost the immunotherapy of hepatocellular carcinoma after microwave ablation. J Control Release. 2024;376:913-29.
109. Yao F, Yuan Q, Yan Y, et al. Yu-Ping-Feng-San improve the immunosuppression of microenvironment in hepatocellular carcinoma by promoting the maturation of DCs through the JAK2-STAT3 pathway. Sci Rep. 2024;14:31522.
110. Li J, Lin W, Huang T, Chen M, Lin Q. IL-12 improves the anti-HCC efficacy of dendritic cells loaded with exosomes from overexpressing Rab27a tumor cells. Exp Cell Res. 2024;439:114073.
111. Wang C, Huang X, Wu Y, Wang J, Li F, Guo G. Tumor cell-associated exosomes robustly elicit anti-tumor immune responses through modulating dendritic cell vaccines in lung tumor. Int J Biol Sci. 2020;16:633-43.
112. Zhang S, Xu H, Li M, et al. An etiology-stratified single-cell atlas identifies FABP4 as a prognostic marker for MASLD-related HCC. J Hepatol. 2026;84:920-32.
113. He J, Liu B, Zhao W, et al. The glucose sensor NSUN2-m5C modification regulates tumor-immune glucose metabolism reprogramming to drive hepatocellular carcinoma evolution. Int J Biol Sci. 2025;21:4529-48.
114. Sun Y, Wu P, Zhang Z, et al. Integrated multi-omics profiling to dissect the spatiotemporal evolution of metastatic hepatocellular carcinoma. Cancer Cell. 2024;42:135-56.e17.
115. Jang EJ, Choi HJ, You YK, et al. Differential infiltration of T-cell populations in tumor and liver tissues predicts recurrence-free survival in surgically resected hepatocellular carcinoma. Cancers. 2025;17:1548.
116. Wu WJ, Wang J, Chen F, et al. Exploration of heterogeneity and recurrence signatures in hepatocellular carcinoma. Mol Oncol. 2025;19:2388-411.
117. Li J, Xu H, Han J, et al. Lymphocyte function in tertiary lymphoid structures predicts hepatocellular carcinoma outcome. Lab Invest. 2024;104:102144.
118. Rennert C, Tauber C, Fehrenbach P, et al. Adaptive subsets limit the anti-tumoral NK-cell activity in hepatocellular carcinoma. Cells. 2021;10:1369.
119. Liu H, Zhao R, Qin R, et al. Panoramic comparison between NK cells in healthy and cancerous liver through single-cell RNA sequencing. Cancer Biol Med. 2022;19:1334-51.
120. Classon P, Wixom AQ, Calixto Mancipe N, et al. Role of long-chain acyl-CoA synthetases in MASH-driven hepatocellular carcinoma and ferroptosis. Am J Physiol Gastrointest Liver Physiol. 2025;329:G571-84.
121. Li S, Zhang J, Wei W, Zhang Z, Huang W, Xia L. The important role of myeloid-derived suppressor cells: from hepatitis to liver cancer. Biochim Biophys Acta Rev Cancer. 2025;1880:189329.
122. Wang H, Zhang H, Wang Y, et al. Regulatory T-cell and neutrophil extracellular trap interaction contributes to carcinogenesis in non-alcoholic steatohepatitis. J Hepatol. 2021;75:1271-83.
123. 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.
124. Shao Y, Lo CM, Ling CC, et al. Regulatory B cells accelerate hepatocellular carcinoma progression via CD40/CD154 signaling pathway. Cancer Lett. 2014;355:264-72.
125. Kotsiliti E, Leone V, Schuehle S, et al. Intestinal B cells license metabolic T-cell activation in NASH microbiota/antigen-independently and contribute to fibrosis by IgA-FcR signalling. J Hepatol. 2023;79:296-313.
126. Lin C, Chen Y, Zhang F, Zhu P, Yu L, Chen W. Single-cell RNA sequencing reveals the mediatory role of cancer-associated fibroblast PTN in hepatitis B virus cirrhosis-HCC progression. Gut Pathog. 2023;15:26.
127. Lu Y, Liu Y, Zuo X, et al. CXCL12+ tumor-associated endothelial cells promote immune resistance in hepatocellular carcinoma. J Hepatol. 2025;82:634-48.
128. Li W, Chen G, Peng H, et al. Research progress on dendritic cells in hepatocellular carcinoma immune microenvironments. Biomolecules. 2024;14:1161.
129. Han Y, Chen Z, Yang Y, et al. Human CD14+ CTLA-4+ regulatory dendritic cells suppress T-cell response by cytotoxic T-lymphocyte antigen-4-dependent IL-10 and indoleamine-2,3-dioxygenase production in hepatocellular carcinoma. Hepatology. 2014;59:567-79.
130. Ma C, Kesarwala AH, Eggert T, et al. NAFLD causes selective CD4+ T lymphocyte loss and promotes hepatocarcinogenesis. Nature. 2016;531:253-7.
131. Li L, Wang H. Heterogeneity of liver cancer and personalized therapy. Cancer Lett. 2016;379:191-7.
132. Ji Z, Li J, Zhang S, Jia Y, Zhang J, Guo Z. The load of hepatitis B virus reduces the immune checkpoint inhibitors efficiency in hepatocellular carcinoma patients. Front Immunol. 2024;15:1480520.
133. Gallage S, Ali A, Barragan Avila JE, et al. A 5:2 intermittent fasting regimen ameliorates NASH and fibrosis and blunts HCC development via hepatic PPARα and PCK1. Cell Metab. 2024;36:1371-93.e7.
134. Lu J, Chan TT, Wang Y, et al. FADD activation in hepatocellular carcinoma potentiates CD8+ T-cell responses and sensitizes to immune checkpoint inhibitors. Cancer Res. 2025;85:3454-70.
135. Gao Y, Gong Y, Song X, et al. Dihydroartemisinin inhibits histone lactylation through YAP1 to act as a ‘hot’ switch for ‘cold’ tumor in hepatocellular carcinoma. Phytomedicine. 2025;148:157307.
136. Xiao R, Tian Y, Zhang J, et al. Increased Siglec-9/Siglec-9L interactions on NK cells predict poor HCC prognosis and present a targetable checkpoint for immunotherapy. J Hepatol. 2024;80:792-804.
137. Jiang Z, Wu Y, Miao Y, et al. HCCDB v2.0: decompose expression variations by single-cell RNA-seq and spatial transcriptomics in HCC. Genomics Proteomics Bioinformatics. 2024;22:qzae011.
138. Dong S, Guo X, Han F, He Z, Wang Y. Emerging role of natural products in cancer immunotherapy. Acta Pharm Sin B. 2022;12:1163-85.
139. Chen ZQ, Zuo XL, Cai J, et al. Hypoxia-associated circPRDM4 promotes immune escape via HIF-1α regulation of PD-L1 in hepatocellular carcinoma. Exp Hematol Oncol. 2023;12:17.
140. Long S, Li M, Chen J, et al. Spatial patterns and MRI-based radiomic prediction of high peritumoral tertiary lymphoid structure density in hepatocellular carcinoma: a multicenter study. J Immunother Cancer. 2024;12:e009879.
141. Li H, Liu H, Fu H, et al. Peritumoral tertiary lymphoid structures correlate with protective immunity and improved prognosis in patients with hepatocellular carcinoma. Front Immunol. 2021;12:648812.
142. Prawira A, Xu H, Mei Y, et al. Targeting Treg-fibroblast interaction to enhance immunotherapy in steatotic liver disease-related hepatocellular carcinoma. Gut. 2025;75:105-18.
143. Wang L, Zhu L, Liang C, et al. Targeting N6-methyladenosine reader YTHDF1 with siRNA boosts antitumor immunity in NASH-HCC by inhibiting EZH2-IL-6 axis. J Hepatol. 2023;79:1185-200.
144. Ringelhan M, Pfister D, O’Connor T, Pikarsky E, Heikenwalder M. The immunology of hepatocellular carcinoma. Nat Immunol. 2018;19:222-32.
145. Li X, Ramadori P, Pfister D, Seehawer M, Zender L, Heikenwalder M. The immunological and metabolic landscape in primary and metastatic liver cancer. Nat Rev Cancer. 2021;21:541-57.
146. Sun Y, Wu L, Zhong Y, et al. Single-cell landscape of the ecosystem in early-relapse hepatocellular carcinoma. Cell. 2021;184:404-21.e16.
147. Calderaro J, Petitprez F, Becht E, et al. Intra-tumoral tertiary lymphoid structures are associated with a low risk of early recurrence of hepatocellular carcinoma. J Hepatol. 2019;70:58-65.
148. Pfister D, Núñez NG, Pinyol R, et al. NASH limits anti-tumour surveillance in immunotherapy-treated HCC. Nature. 2021;592:450-6.
149. Chen DP, Ning WR, Jiang ZZ, et al. Glycolytic activation of peritumoral monocytes fosters immune privilege via the PFKFB3-PD-L1 axis in human hepatocellular carcinoma. J Hepatol. 2019;71:333-43.
150. Cappuyns S, Piqué-Gili M, Esteban-Fabró R, et al. Single-cell RNA sequencing-derived signatures define response patterns to atezolizumab + bevacizumab in advanced hepatocellular carcinoma. J Hepatol. 2025;82:1036-49.
151. Fulgenzi CAM, Cheon J, D’Alessio A, et al. Reproducible safety and efficacy of atezolizumab plus bevacizumab for HCC in clinical practice: results of the AB-real study. Eur J Cancer. 2022;175:204-13.
152. Gordan JD, Kennedy EB, Abou-Alfa GK, et al. Systemic therapy for advanced hepatocellular carcinoma: ASCO guideline update. J Clin Oncol. 2024;42:1830-50.
153. Shayan G, Srivastava R, Li J, Schmitt N, Kane LP, Ferris RL. Adaptive resistance to anti-PD1 therapy by Tim-3 upregulation is mediated by the PI3K-Akt pathway in head and neck cancer. Oncoimmunology. 2017;6:e1261779.
154. Johnston RJ, Comps-Agrar L, Hackney J, et al. The immunoreceptor TIGIT regulates antitumor and antiviral CD8+ T cell effector function. Cancer Cell. 2014;26:923-37.
155. Kim TK, Han X, Hu Q, et al. PD-1H/VISTA mediates immune evasion in acute myeloid leukemia. J Clin Invest. 2024;134:e164325.
156. Schaafsma E, Croteau W, ElTanbouly M, et al. VISTA targeting of T-cell quiescence and myeloid suppression overcomes adaptive resistance. Cancer Immunol Res. 2023;11:38-55.
157. Zhang J, Yin Y, Tang J, Zhang Y, Tian Y, Sun F. Changes in serum interleukin-8 levels predict response to immune checkpoint inhibitors immunotherapy in unresectable hepatocellular carcinoma patients. J Inflamm Res. 2024;17:3397-406.
158. Hong C, Dong HZ, Li RN, et al. Predictive value of the hepatic immune predictive index for patients with primary liver cancer treated with immune checkpoint inhibitors. Dig Dis. 2023;41:422-30.
159. Hung HC, Lee JC, Wang YC, et al. Response prediction in immune checkpoint inhibitor immunotherapy for advanced hepatocellular carcinoma. Cancers. 2021;13:1607.
160. Yuen VW, Chiu DK, Law CT, et al. Using mouse liver cancer models based on somatic genome editing to predict immune checkpoint inhibitor responses. J Hepatol. 2023;78:376-89.
161. Budhu A, Pehrsson EC, He A, et al. Tumor biology and immune infiltration define primary liver cancer subsets linked to overall survival after immunotherapy. Cell Rep Med. 2023;4:101052.
162. Ren Z, Wang Y, Jiang D, et al. PD1+ Treg cell remodeling promotes immune homeostasis within peripheral blood and tumor microenvironment after microparticles-transarterial chemoembolization in hepatocellular carcinoma. Cancer Immunol Immunother. 2025;74:109.
163. Yang P, Qin H, Li Y, et al. CD36-mediated metabolic crosstalk between tumor cells and macrophages affects liver metastasis. Nat Commun. 2022;13:5782.
164. Liu QQ, Li HZ, Li SX, et al. CD36-mediated accumulation of MDSCs exerts abscopal immunosuppressive responses in hepatocellular carcinoma after insufficient microwave ablation. Biochim Biophys Acta Mol Basis Dis. 2024;1870:167493.
165. Wang F, You H, Liu H, et al. Silencing PTPN2 with nanoparticle-delivered small interfering RNA remodels tumor microenvironment to sensitize immunotherapy in hepatocellular carcinoma. Acta Pharm Sin B. 2025;15:2915-29.
166. Liu Y, Yang S, Zhou Q, et al. Nanobubble-based anti-hepatocellular carcinoma therapy combining immune check inhibitors and sonodynamic therapy. Nanoscale Adv. 2022;4:4847-62.
167. Yang Y, Pei T, Hu X, et al. Dietary vitamin B3 supplementation induces the antitumor immunity against liver cancer via biased GPR109A signaling in myeloid cell. Cell Rep Med. 2024;5:101718.
168. Liu Q, Liang Z, Wang J, et al. Mannose-modified multifunctional iron-based nanozyme for hepatocellular carcinoma treatment by remodeling the tumor microenvironment. Colloids Surf B Biointerfaces. 2025;250:114548.
169. Yan Y, Hu J, Han N, et al. Sorafenib-loaded metal-organic framework nanoparticles for anti-hepatocellular carcinoma effects through synergistically potentiating ferroptosis and remodeling tumor immune microenvironment. Mater Today Bio. 2025;32:101848.
170. Kong M, Qiu L. Coordinated modulation of glucose metabolism and immunity via metal-drug nanovesicles for hepatocellular carcinoma therapy. J Control Release. 2025;384:113957.
171. Hu H, Ning S, Liu F, et al. Hafnium metal-organic framework-based glutamine metabolism disruptor for potentiating radio-immunotherapy in MYC-amplified hepatocellular carcinoma. ACS Appl Mater Interfaces. 2025;17:19367-81.
172. Nie Y. Breaking barriers: the emerging promise of CAR-T cell therapy in solid tumors. Holist Integ Oncol. 2025;4:205.
173. Liu H, Xu Y, Xiang J, et al. Targeting alpha-fetoprotein (AFP)-MHC complex with CAR T-cell therapy for liver cancer. Clin Cancer Res. 2017;23:478-88.
174. Sun L, Gao F, Gao Z, et al. Shed antigen-induced blocking effect on CAR-T cells targeting Glypican-3 in Hepatocellular Carcinoma. J Immunother Cancer. 2021;9:e001875.
175. Steffin D, Ghatwai N, Montalbano A, et al. Interleukin-15-armoured GPC3 CAR T cells for patients with solid cancers. Nature. 2025;637:940-6.
176. Shi D, Shi Y, Kaseb AO, et al. Chimeric antigen receptor-glypican-3 T-cell therapy for advanced hepatocellular carcinoma: results of phase I trials. Clin Cancer Res. 2020;26:3979-89.
177. Yang Z, Cheng C, Li Z, et al. Advancing liver cancer treatment with dual-targeting CAR-T therapy. J Nanobiotechnology. 2025;23:462.
178. Niu X, Zhang P, Dai L, et al. Flagellin engineering enhances CAR-T cell function by reshaping tumor microenvironment in solid tumors. J Immunother Cancer. 2025;13:e010237.
179. Nishimoto KP, Lamture G, Chanthery Y, et al. ADI-270: an armored allogeneic gamma delta T cell therapy designed to target CD70-expressing solid and hematologic malignancies. J Immunother Cancer. 2025;13:e011704.
180. Gattinoni L, Finkelstein SE, Klebanoff CA, et al. Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells. J Exp Med. 2005;202:907-12.
181. Mullinax JE, Hall M, Prabhakaran S, et al. Combination of ipilimumab and adoptive cell therapy with tumor-infiltrating lymphocytes for patients with metastatic melanoma. Front Oncol. 2018;8:44.
182. Rosenberg SA, Yang JC, Sherry RM, et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res. 2011;17:4550-7.
183. Park H, Kim G, Kim N, Ha S, Yim H. Efficacy and safety of natural killer cell therapy in patients with solid tumors: a systematic review and meta-analysis. Front Immunol. 2024;15:1454427.
184. Fujisaki H, Kakuda H, Shimasaki N, et al. Expansion of highly cytotoxic human natural killer cells for cancer cell therapy. Cancer Res. 2009;69:4010-7.
185. Zhang Y, Wallace DL, de Lara CM, et al. In vivo kinetics of human natural killer cells: the effects of ageing and acute and chronic viral infection. Immunology. 2007;121:258-65.
186. Zhao X, Zhao B, Sun Y, Liu A. CAR-exosomes derived from immune cells: an emerging nanoscale vanguard in overcoming tumor immunotherapy hurdles. Front Immunol. 2025;16:1655095.
187. Tong T, Gao W, Jian H, et al. The role and potential mechanisms of exosomes in the progression of hepatocellular carcinoma. Holist Integ Oncol. 2025;4:171.
189. Quinn WJ 3rd, Jiao J, TeSlaa T, et al. Lactate limits T cell proliferation via the NAD(H) redox state. Cell Rep. 2020;33:108500.
190. Bohn T, Rapp S, Luther N, et al. Tumor immunoevasion via acidosis-dependent induction of regulatory tumor-associated macrophages. Nat Immunol. 2018;19:1319-29.
191. Colegio OR, Chu NQ, Szabo AL, et al. Functional polarization of tumour-associated macrophages by tumour-derived lactic acid. Nature. 2014;513:559-63.
192. Jiang L, Shen Y, Feng Z, et al. The multidimensional role of SLC16A4 in hepatocellular carcinoma in silico analysis: prognostic significance, metabolic pathways, and immune microenvironment regulation. Eur J Med Res. 2025;30:1007.
193. Shen J, Wu Z, Zhou Y, et al. Knockdown of SLC16A3 decreases extracellular lactate concentration in hepatocellular carcinoma, alleviates hypoxia and induces ferroptosis. Biochem Biophys Res Commun. 2024;733:150709.
194. Li J, Zhang Y, Deng J, et al. Cross-talk between lactate metabolism and immunity reveals CEP55 as a potential regulator in the immunosuppressive microenvironment of hepatocellular carcinoma. Genes Dis. 2025;12:101399.
195. Ding CH, Yan FZ, Xu BN, et al. PRMT3 drives PD-L1-mediated immune escape through activating PDHK1-regulated glycolysis in hepatocellular carcinoma. Cell Death Dis. 2025;16:158.
196. Che Y, Chen G, Guo Q, Duan Y, Feng H, Xia Q. Gut microbial metabolite butyrate improves anticancer therapy by regulating intracellular calcium homeostasis. Hepatology. 2023;78:88-102.
197. McBrearty N, Arzumanyan A, Bichenkov E, Merali S, Merali C, Feitelson M. Short chain fatty acids delay the development of hepatocellular carcinoma in HBx transgenic mice. Neoplasia. 2021;23:529-38.
198. Yan F, Zhang Q, Shi K, et al. Gut microbiota dysbiosis with hepatitis B virus liver disease and association with immune response. Front Cell Infect Microbiol. 2023;13:1152987.
199. Huo R, Chen Y, Li J, et al. Altered gut microbiota composition and its potential association in patients with advanced hepatocellular carcinoma. Curr Oncol. 2023;30:1818-30.
200. DeFilipp Z, Peled JU, Li S, et al. Third-party fecal microbiota transplantation following allo-HCT reconstitutes microbiome diversity. Blood Adv. 2018;2:745-53.
201. Tanoue T, Morita S, Plichta DR, et al. A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. Nature. 2019;565:600-5.
202. Oh B, Boyle F, Pavlakis N, et al. The gut microbiome and cancer immunotherapy: can we use the gut microbiome as a predictive biomarker for clinical response in cancer immunotherapy? Cancers. 2021;13:4824.
203. Wu H, Zheng X, Pan T, et al. Dynamic microbiome and metabolome analyses reveal the interaction between gut microbiota and anti-PD-1 based immunotherapy in hepatocellular carcinoma. Int J Cancer. 2022;151:1321-34.
204. Matsubara T, Tanaka N, Patterson AD, Cho JY, Krausz KW, Gonzalez FJ. Lithocholic acid disrupts phospholipid and sphingolipid homeostasis leading to cholestasis in mice. Hepatology. 2011;53:1282-93.
205. Varanasi SK, Chen D, Liu Y, et al. Bile acid synthesis impedes tumor-specific T cell responses during liver cancer. Science. 2025;387:192-201.
206. Kudo M. A new era in systemic therapy for hepatocellular carcinoma: atezolizumab plus bevacizumab combination therapy. Liver Cancer. 2020;9:119-37.
207. Liu ZL, Zhu LL, Liu JH, Pu ZY, Ruan ZP, Chen J. Vascular endothelial growth factor receptor-2 and its association with tumor immune regulatory gene expression in hepatocellular carcinoma. Aging. 2020;12:25172-88.
208. Liu D, Song T. Advances in neoadjuvant therapy for hepatocellular carcinoma. Holist Integ Oncol. 2025;4:173.
209. Chiang CL, Chiu KWH, Chan KSK, et al. Sequential transarterial chemoembolisation and stereotactic body radiotherapy followed by immunotherapy as conversion therapy for patients with locally advanced, unresectable hepatocellular carcinoma (START-FIT): a single-arm, phase 2 trial. Lancet Gastroenterol Hepatol. 2023;8:169-78.
210. Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68:723-50.
211. Kim KJ, Kim JH, Lee SJ, Lee EJ, Shin EC, Seong J. Radiation improves antitumor effect of immune checkpoint inhibitor in murine hepatocellular carcinoma model. Oncotarget. 2017;8:41242-55.
212. Kim HJ, Park S, Kim KJ, Seong J. Clinical significance of soluble programmed cell death ligand-1 (sPD-L1) in hepatocellular carcinoma patients treated with radiotherapy. Radiother Oncol. 2018;129:130-5.
213. Behm B, Di Fazio P, Michl P, et al. Additive antitumour response to the rabbit VX2 hepatoma by combined radio frequency ablation and toll like receptor 9 stimulation. Gut. 2016;65:134-43.
214. Xie C, Duffy AG, Mabry-Hrones D, et al. Tremelimumab in combination with microwave ablation in patients with refractory biliary tract cancer. Hepatology. 2019;69:2048-60.
215. Zhang X, Zhu F, Wen J, Pan Z, Zhu Y. Factors influencing the timing of second-line therapy for the treatment of advanced hepatocellular carcinoma: a systematic review and meta-analysis. Holist Integ Oncol. 2025;4:179.
216. Kimura T, Kato Y, Ozawa Y, et al. Immunomodulatory activity of lenvatinib contributes to antitumor activity in the Hepa1-6 hepatocellular carcinoma model. Cancer Sci. 2018;109:3993-4002.
217. Xie F, Chen B, Yang X, et al. Efficacy of immune checkpoint inhibitors plus molecular targeted agents after the progression of lenvatinib for advanced hepatocellular carcinoma. Front Immunol. 2022;13:1052937.
218. Wu R, Xiong J, Zhou T, et al. Quercetin/anti-PD-1 antibody combination therapy regulates the gut microbiota, impacts macrophage immunity and reshapes the hepatocellular carcinoma tumor microenvironment. Front Biosci. 2023;28:327.
219. Conche C, Finkelmeier F, Pešić M, et al. Combining ferroptosis induction with MDSC blockade renders primary tumours and metastases in liver sensitive to immune checkpoint blockade. Gut. 2023;72:1774-82.
220. Liu HY, Pedros C, Kong KF, Canonigo-Balancio AJ, Xue W, Altman A. Leveraging the Treg-intrinsic CTLA4-PKCη signaling pathway for cancer immunotherapy. J Immunother Cancer. 2021;9:e002792.
221. Qiu Y, Wu Z, Chen Y, et al. Nano ultrasound contrast agent for synergistic chemo-photothermal therapy and enhanced immunotherapy against liver cancer and metastasis. Adv Sci. 2023;10:e2300878.
222. Yuan Y, Chen Y, Huang C, et al. Efficacy and safety of radiotherapy combined with immunotherapy and targeted therapy versus immunotherapy plus targeted therapy alone in unresectable hepatocellular carcinoma: a retrospective study. Front Oncol. 2025;15:1643304.
223. Yang H, Cong T, Luo Y, Yang C, Ren J, Li X. Prognostic effect of sarcopenia in hepatocellular carcinoma patients targeted with interventional therapy combined with immunotherapy and targeted therapy. J Hepatocell Carcinoma. 2024;11:175-89.
224. Sharma R, Pillai A, Marron TU, et al. Patterns and outcomes of subsequent therapy after immune checkpoint inhibitor discontinuation in HCC. Hepatol Commun. 2022;6:1776-85.
225. Andreata F, Laura C, Ravà M, et al. Therapeutic potential of co-signaling receptor modulation in hepatitis B. Cell. 2024;187:4078-94.e21.
226. Li FJ, Zhang Y, Jin GX, Yao L, Wu DQ. Expression of LAG-3 is coincident with the impaired effector function of HBV-specific CD8+ T cell in HCC patients. Immunol Lett. 2013;150:116-22.
227. Shi J, Li G, Liu L, et al. Establishment and validation of exhausted CD8+ T cell feature as a prognostic model of HCC. Front Immunol. 2023;14:1166052.
228. Liu M, Li L, Cao L, et al. Targeted delivery of CCL3 reprograms macrophage antigen presentation and enhances the efficacy of immune checkpoint blockade therapy in hepatocellular carcinoma. J Immunother Cancer. 2025;13:e010947.
229. Yang F, Hilakivi-Clarke L, Shaha A, et al. Metabolic reprogramming and its clinical implication for liver cancer. Hepatology. 2023;78:1602-24.
230. Huang Y, Xie Y, Zhang Y, et al. Single-cell transcriptome reveals the reprogramming of immune microenvironment during the transition from MASH to HCC. Mol Cancer. 2025;24:177.
231. Thimme R, Neumann-Haefelin C. T cells engineered to carry a high-affinity HBV-specific T cell receptor: a potent weapon against advanced HBV-related HCC. Gut. 2025;Epub ahead of print.
232. Zhu W, Zhang Z, Chen J, et al. A novel engineered IL-21 receptor arms T-cell receptor-engineered T cells (TCR-T cells) against hepatocellular carcinoma. Signal Transduct Target Ther. 2024;9:101.
233. Bae WK, Lee BC, Kim HJ, et al. A phase I study of locoregional high-dose autologous natural killer cell therapy with hepatic arterial infusion chemotherapy in patients with locally advanced hepatocellular carcinoma. Front Immunol. 2022;13:879452.
234. Cheng Y, Gong Y, Chen X, et al. Injectable adhesive hemostatic gel with tumor acidity neutralizer and neutrophil extracellular traps lyase for enhancing adoptive NK cell therapy prevents post-resection recurrence of hepatocellular carcinoma. Biomaterials. 2022;284:121506.
235. Hu X, Shui Y, Shimizu S, et al. Targeted immune cell therapy for hepatocellular carcinoma using expanded liver mononuclear cell-derived natural killer cells. Neoplasia. 2024;58:101061.
236. Chen QT, Zhang ZY, Huang QL, et al. HK1 from hepatic stellate cell-derived extracellular vesicles promotes progression of hepatocellular carcinoma. Nat Metab. 2022;4:1306-21.
237. Huang X, Yang J, Hu Y, et al. Protective effects of GalNac-modified red blood cell-derived extracellular vesicles against liver diseases. Int J Nanomedicine. 2025;20:8993-9017.
238. Yang K, Wang X, Song C, et al. The role of lipid metabolic reprogramming in tumor microenvironment. Theranostics. 2023;13:1774-808.
239. Yao H, Ma S, Huang J, et al. Trojan-horse strategy targeting the gut-liver axis modulates gut microbiome and reshapes microenvironment for orthotopic hepatocellular carcinoma therapy. Adv Sci. 2024;11:e2310002.
240. Li Z, Zhang Y, Hong W, et al. Gut microbiota modulate radiotherapy-associated antitumor immune responses against hepatocellular carcinoma Via STING signaling. Gut Microbes. 2022;14:2119055.
241. Tan J, Fang J, Luo W, et al. Co-delivery of chemotherapy and anti-angiogenic lipid via DPPA-LNPs potentiates anti-PD-1 immunotherapy. Int J Nanomedicine. 2025;20:14057-73.
242. Xian F, Wu C, Zhang G, Xu G. Efficacy and safety of immune checkpoint inhibitors combined anti-angiogenic therapy in patients with unresectable hepatocellular carcinoma: a meta-analysis. Medicine. 2022;101:e31479.
243. Jin ZC, Chen JJ, Zhu XL, et al. ; CHANCE2201 Investigators. Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study. EClinicalMedicine. 2024;72:102622.
