REFERENCES

1. Villanueva A. Hepatocellular carcinoma. N Engl J Med 2019;380:1450-62.

2. Islami F, Ward EM, Sung H, et al. Annual report to the nation on the status of cancer, part 1: national cancer statistics. J Natl Cancer Inst 2021;113:1648-69.

3. Ju MR, Yopp AC. Surgical resection of early stage hepatocellular carcinoma: balancing tumor biology with the host liver. Chin Clin Oncol 2021;10:5.

4. Roxburgh P, Evans TR. Systemic therapy of hepatocellular carcinoma: are we making progress? Adv Ther 2008;25:1089-104.

5. Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet 2012;379:1245-55.

6. Tang J, Sui CJ, Wang DF, et al. Targeted sequencing reveals the mutational landscape responsible for sorafenib therapy in advanced hepatocellular carcinoma. Theranostics 2020;10:5384-97.

7. Clarke MF, Dick JE, Dirks PB, et al. Cancer stem cells-perspectives on current status and future directions: AACR wrkshop on cancer stem cells. Cancer Res 2006;66:9339-44.

8. Xiang Y, Yang T, Pang BY, Zhu Y, Liu YN. The progress and prospects of putative biomarkers for liver cancer stem cells in hepatocellular carcinoma. Stem Cells Int 2016;2016:7614971.

9. Ruiu R, Tarone L, Rolih V, et al. Cancer stem cell immunology and immunotherapy: Harnessing the immune system against cancer’s source. Cancer Immunotherapy. Elsevier; 2019. p. 119-88.

10. Lo Re O, Mazza T, Giallongo S, et al. Loss of histone macroH2A1 in hepatocellular carcinoma cells promotes paracrine-mediated chemoresistance and CD4+CD25+FoxP3+ regulatory T cells activation. Theranostics 2020;10:910-24.

11. Park DJ, Sung PS, Kim JH, et al. EpCAM-high liver cancer stem cells resist natural killer cell-mediated cytotoxicity by upregulating CEACAM1. J Immunother Cancer 2020;8:e000301.

12. Cheung PF, Yip CW, Wong NC, et al. Granulin-epithelin precursor renders hepatocellular carcinoma cells resistant to natural killer cytotoxicity. Cancer Immunol Res 2014;2:1209-19.

13. Lee TK, Guan XY, Ma S. Cancer stem cells in hepatocellular carcinoma - from origin to clinical implications. Nat Rev Gastroenterol Hepatol 2022;19:26-44.

14. 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.

15. Sperandio RC, Pestana RC, Miyamura BV, Kaseb AO. Hepatocellular carcinoma immunotherapy. Annu Rev Med 2022;73:267-78.

16. Kreso A, Dick JE. Evolution of the cancer stem cell model. Cell Stem Cell 2014;14:275-91.

17. Farhood B, Najafi M, Mortezaee K. CD8+ cytotoxic T lymphocytes in cancer immunotherapy: a review. J Cell Physiol 2019;234:8509-21.

18. Bian J, Lin J, Long J et al. T lymphocytes in hepatocellular carcinoma immune microenvironment: insights into human immunology and immunotherapy. Am J Cancer Res 2020;10:4585-606.

19. Bálint Š, Müller S, Fischer R, et al. Supramolecular attack particles are autonomous killing entities released from cytotoxic T cells. Science 2020;368:897-901.

20. Logtenberg MEW, Scheeren FA, Schumacher TN. The CD47-SIRPα immune checkpoint. Immunity 2020;52:742-52.

21. Chiu DK, Yuen VW, Cheu JW, et al. Hepatocellular carcinoma cells up-regulate PVRL1, stabilizing PVR and inhibiting the cytotoxic T-Cell response via TIGIT to mediate tumor resistance to PD1 inhibitors in mice. Gastroenterology 2020;159:609-23.

22. Jansen CS, Prokhnevska N, Master VA, et al. An intra-tumoral niche maintains and differentiates stem-like CD8 T cells. Nature 2019;576:465-70.

23. Zheng C, Zheng L, Yoo JK, et al. Landscape of infiltrating T cells in liver cancer revealed by single-cell sequencing. Cell 2017;169:1342-1356.e16.

24. Yang Y, Liu F, Liu W, et al. Analysis of single-cell RNAseq identifies transitional states of T cells associated with hepatocellular carcinoma. Clin Transl Med 2020;10:e133.

25. Wang X, He Q, Shen H, et al. TOX promotes the exhaustion of antitumor CD8+ T cells by preventing PD1 degradation in hepatocellular carcinoma. J Hepatol 2019;71:731-41.

26. Barsch M, Salié H, Schlaak AE, et al. T-cell exhaustion and residency dynamics inform clinical outcomes in hepatocellular carcinoma. J Hepatol 2022;77:397-409.

27. McLane LM, Abdel-Hakeem MS, Wherry EJ. CD8 T cell exhaustion during chronic viral infection and cancer. Annu Rev Immunol 2019;37:457-95.

28. Zhou G, Sprengers D, Boor PPC, et al. Antibodies against immune checkpoint molecules restore functions of tumor-infiltrating T Cells in hepatocellular carcinomas. Gastroenterology 2017;153:1107-1119.e10.

29. Wu Q, Zhou W, Yin S, et al. Blocking triggering receptor expressed on myeloid cells-1-positive tumor-associated macrophages induced by hypoxia reverses immunosuppression and anti-programmed cell death ligand 1 resistance in liver cancer. Hepatology 2019;70:198-214.

30. Tao H, Liu M, Wang Y, et al. Icaritin induces anti-tumor immune responses in hepatocellular carcinoma by inhibiting splenic myeloid-derived suppressor cell generation. Front Immunol 2021;12:609295.

31. Morrison BJ, Steel JC, Morris JC. Reduction of MHC-I expression limits T-lymphocyte-mediated killing of Cancer-initiating cells. BMC Cancer 2018;18:469.

32. Guo X, Zhao Y, Yan H, et al. Single tumor-initiating cells evade immune clearance by recruiting type II macrophages. Genes Dev 2017;31:247-59.

33. Gupta HB, Clark CA, Yuan B, et al. Tumor cell-intrinsic PD-L1 promotes tumor-initiating cell generation and functions in melanoma and ovarian cancer. Signal Transduct Target Ther 2016;1:16030.

34. Nishida N, Sakai K, Morita M, et al. Association between genetic and immunological background of hepatocellular carcinoma and expression of programmed cell death-1. Liver Cancer 2020;9:426-39.

35. Kaufhold S, Garbán H, Bonavida B. Yin Yang 1 is associated with cancer stem cell transcription factors (SOX2, OCT4, BMI1) and clinical implication. J Exp Clin Cancer Res 2016;35:84.

36. Zhong F, Cheng X, Sun S, Zhou J. Transcriptional activation of PD-L1 by Sox2 contributes to the proliferation of hepatocellular carcinoma cells. Oncol Rep 2017;37:3061-7.

37. Chan LC, Li CW, Xia W, et al. IL-6/JAK1 pathway drives PD-L1 Y112 phosphorylation to promote cancer immune evasion. J Clin Invest 2019;129:3324-38.

38. Huang CY, Wang Y, Luo GY, et al. Relationship between PD-L1 expression and CD8+ T-cell immune responses in hepatocellular carcinoma. J Immunother 2017;40:323-33.

39. Pan K, Zhao JJ, Wang H, et al. Comparative analysis of cytotoxic T lymphocyte response induced by dendritic cells loaded with hepatocellular carcinoma -derived RNA or cell lysate. Int J Biol Sci 2010;6:639-48.

40. Shibolet O, Alper R, Zlotogarov L, et al. NKT and CD8 lymphocytes mediate suppression of hepatocellular carcinoma growth via tumor antigen-pulsed dendritic cells. Int J Cancer 2003;106:236-43.

41. Yamashita T, Ji J, Budhu A, et al. EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Gastroenterology 2009;136:1012-24.

42. Ruiz de Galarreta M, Bresnahan E, Molina-Sánchez P, et al. β-catenin activation promotes immune escape and resistance to Anti-PD-1 therapy in hepatocellular carcinoma. Cancer Discov 2019;9:1124-41.

43. Pardee AD, Shi J, Butterfield LH. Tumor-derived α-fetoprotein impairs the differentiation and T cell stimulatory activity of human dendritic cells. The Journal of Immunology 2014;193:5723-32.

44. Pan QZ, Pan K, Wang QJ, et al. Annexin A3 as a potential target for immunotherapy of liver cancer stem-like cells. Stem Cells 2015;33:354-66.

45. Chen X, Du Y, Huang Z. CD4+CD25+ Treg derived from hepatocellular carcinoma mice inhibits tumor immunity. Immunology Letters 2012;148:83-9.

46. Kryczek I, Liu R, Wang G, et al. FOXP3 Defines regulatory T cells in human tumor and autoimmune disease. Cancer Research 2009;69:3995-4000.

47. Cabrera R, Ararat M, Eksioglu EA, et al. Influence of serum and soluble CD25 (sCD25) on regulatory and effector T-cell function in hepatocellular carcinoma. Scand J Immunol 2010;72:293-301.

48. Ormandy LA, Hillemann T, Wedemeyer H, Manns MP, Greten TF, Korangy F. Increased populations of regulatory T cells in peripheral blood of patients with hepatocellular carcinoma. Cancer Res 2005;65:2457-64.

49. Santoiemma PP, Powell DJ Jr. Tumor infiltrating lymphocytes in ovarian cancer. Cancer Biol Ther 2015;16:807-20.

50. Pedroza-Gonzalez A, Verhoef C, Ijzermans JN, et al. Activated tumor-infiltrating CD4+ regulatory T cells restrain antitumor immunity in patients with primary or metastatic liver cancer. Hepatology 2013;57:183-94.

51. Fu J, Xu D, Liu Z, et al. Increased regulatory T cells correlate with CD8 T-cell impairment and poor survival in hepatocellular carcinoma patients. Gastroenterology 2007;132:2328-39.

52. Jiang R, Tang J, Chen Y, et al. The long noncoding RNA lnc-EGFR stimulates T-regulatory cells differentiation thus promoting hepatocellular carcinoma immune evasion. Nat Commun 2017;8:15129.

53. Suthen S, Lim CJ, Nguyen PHD, et al. Hypoxia-driven immunosuppression by Treg and type-2 conventional dendritic cells in HCC. Hepatology 2022;76:1329-44.

54. Wang Z, He L, Li W, et al. GDF15 induces immunosuppression via CD48 on regulatory T cells in hepatocellular carcinoma. J Immunother Cancer 2021;9:e002787.

55. Watson MJ, Vignali PDA, Mullett SJ, et al. Metabolic support of tumour-infiltrating regulatory T cells by lactic acid. Nature 2021;591:645-51.

56. Zhou Y, Wang B, Wu J, et al. Association of preoperative EpCAM Circulating Tumor Cells and peripheral Treg cell levels with early recurrence of hepatocellular carcinoma following radical hepatic resection. BMC Cancer 2016;16:506.

57. Cao W, Li M, Liu J, et al. LGR5 marks targetable tumor-initiating cells in mouse liver cancer. Nat Commun 2020;11:1961.

58. Ko CJ, Li CJ, Wu MY, Chu PY. Overexpression of LGR-5 as a Predictor of Poor Outcome in Patients with Hepatocellular Carcinoma. Int J Environ Res Public Health 2019;16:1836.

59. Liu XS, Lin XK, Mei Y, et al. Regulatory T cells promote overexpression of Lgr5 on gastric cancer cells via TGF-beta1 and confer poor prognosis in gastric cancer. Front Immunol 2019;10:1741.

60. Mima K, Okabe H, Ishimoto T, et al. CD44s regulates the TGF-β-mediated mesenchymal phenotype and is associated with poor prognosis in patients with hepatocellular carcinoma. Cancer Res 2012;72:3414-23.

61. Yang P, Li QJ, Feng Y, et al. TGF-β-miR-34a-CCL22 signaling-induced Treg cell recruitment promotes venous metastases of HBV-positive hepatocellular carcinoma. Cancer Cell 2012;22:291-303.

62. Sun C, Sun H, Zhang C, Tian Z. NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma. Cell Mol Immunol 2015;12:292-302.

63. Liu P, Chen L, Zhang H. Natural killer cells in liver disease and hepatocellular carcinoma and the NK cell-based immunotherapy. J Immunol Res 2018;2018:1206737.

64. Jinushi M, Takehara T, Tatsumi T, et al. Impairment of natural killer cell and dendritic cell functions by the soluble form of MHC class I-related chain A in advanced human hepatocellular carcinomas. J Hepatol 2005;43:1013-20.

65. Cadoux M, Caruso S, Pham S, et al. Expression of NKG2D ligands is downregulated by β-catenin signalling and associates with HCC aggressiveness. J Hepatol 2021;74:1386-97.

66. Rong XX, Wei F, Lin XL, et al. Recognition and killing of cancer stem-like cell population in hepatocellular carcinoma cells by cytokine-induced killer cells via NKG2d-ligands recognition. Oncoimmunology 2016;5:e1086060.

67. Cheung PF, Cheng CK, Wong NC, et al. Granulin-epithelin precursor is an oncofetal protein defining hepatic cancer stem cells. PLoS One 2011;6:e28246.

68. Cheung PF, Yip CW, Ng LW, et al. Restoration of natural killer activity in hepatocellular carcinoma by treatment with antibody against granulin-epithelin precursor. Oncoimmunology 2015;4:e1016706.

69. Zhao H, Jia H, Han Q, Zhang J. Homeobox containing 1 inhibits liver cancer progression by promoting autophagy as well as inhibiting stemness and immune escape. Oncol Rep 2018;40:1657-65.

70. Weng J, Han X, Liu K, et al. CD44 3'-Untranslated region functions as a competing endogenous RNA to enhance NK sensitivity of liver cancer stem cell by regulating ULBP2 expression. Int J Biol Sci 2019;15:1664-75.

71. Sautès-Fridman C, Lawand M, Giraldo NA, et al. Tertiary lymphoid structures in cancers: prognostic value, regulation, and manipulation for therapeutic intervention. Front Immunol 2016;7:407.

72. Schumacher TN, Thommen DS. Tertiary lymphoid structures in cancer. Science 2022;375:eabf9419.

73. Fridman WH, Zitvogel L, Sautès-Fridman C, Kroemer G. The immune contexture in cancer prognosis and treatment. Nat Rev Clin Oncol 2017;14:717-34.

74. Finkin S, Yuan D, Stein I, et al. Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma. Nat Immunol 2015;16:1235-44.

75. 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.

76. Wu R, Guo W, Qiu X, et al. Comprehensive analysis of spatial architecture in primary liver cancer. Sci Adv 2021;7:eabg3750.

77. Li L, Hao X, Qin J, et al. Antibody against CD44s inhibits pancreatic tumor initiation and postradiation recurrence in mice. Gastroenterology 2014;146:1108-18.

78. Chen H, Luo Z, Sun W, et al. Low glucose promotes CD133mAb-elicited cell death via inhibition of autophagy in hepatocarcinoma cells. Cancer Letters 2013;336:204-12.

79. Chetty C, Khumalo T, Da Costa Dias B, et al. Anti-LRP/LR specific antibody IgG1-iS18 impedes adhesion and invasion of liver cancer cells. PLoS One 2014;9:e96268.

80. Zhao W, Wang L, Han H, et al. 1B50-1, a mAb raised against recurrent tumor cells, targets liver tumor-initiating cells by binding to the calcium channel α2δ1 subunit. Cancer Cell 2013;23:541-56.

81. Tong M, Fung TM, Luk ST, et al. ANXA3/JNK signaling promotes self-renewal and tumor growth, and its blockade provides a therapeutic target for hepatocellular carcinoma. Stem Cell Reports 2015;5:45-59.

82. Tong M, Che N, Zhou L, et al. Efficacy of annexin A3 blockade in sensitizing hepatocellular carcinoma to sorafenib and regorafenib. J Hepatol 2018;69:826-39.

83. Suda T, Yamashita T, Sunagozaka H, et al. Dickkopf-1 promotes angiogenesis and is a biomarker for hepatic stem cell-like hepatocellular carcinoma. Int J Mol Sci 2022;23:2801.

84. Chao MP, Weissman IL, Majeti R. The CD47-SIRPα pathway in cancer immune evasion and potential therapeutic implications. Curr Opin Immunol 2012;24:225-32.

85. Lee TK, Cheung VC, Lu P, et al. Blockade of CD47-mediated cathepsin S/protease-activated receptor 2 signaling provides a therapeutic target for hepatocellular carcinoma. Hepatology 2014;60:179-91.

86. Xiao Z, Chung H, Banan B, et al. Antibody mediated therapy targeting CD47 inhibits tumor progression of hepatocellular carcinoma. Cancer Lett 2015;360:302-9.

87. Lo J, Lau EY, So FT, et al. Anti-CD47 antibody suppresses tumour growth and augments the effect of chemotherapy treatment in hepatocellular carcinoma. Liver Int 2016;36:737-45.

88. Lo J, Lau EY, Ching RH, et al. Nuclear factor kappa B-mediated CD47 up-regulation promotes sorafenib resistance and its blockade synergizes the effect of sorafenib in hepatocellular carcinoma in mice. Hepatology 2015;62:534-45.

89. Du K, Li Y, Liu J, et al. A bispecific antibody targeting GPC3 and CD47 induced enhanced antitumor efficacy against dual antigen-expressing HCC. Mol Ther 2021;29:1572-84.

90. Soto-Pantoja DR, Terabe M, Ghosh A, et al. CD47 in the tumor microenvironment limits cooperation between antitumor T-cell immunity and radiotherapy. Cancer Res 2014;74:6771-83.

91. Murali M, Kumar AR, Nair B, et al. Antibody-drug conjugate as targeted therapeutics against hepatocellular carcinoma: preclinical studies and clinical relevance. Clin Transl Oncol 2022;24:407-31.

92. He H, Tu X, Zhang J, et al. A novel antibody targeting CD24 and hepatocellular carcinoma in vivo by near-infrared fluorescence imaging. Immunobiology 2015;220:1328-36.

93. Ma Z, He H, Sun F, et al. Selective targeted delivery of doxorubicin via conjugating to anti-CD24 antibody results in enhanced antitumor potency for hepatocellular carcinoma both in vitro and in vivo. J Cancer Res Clin Oncol 2017;143:1929-40.

94. Sun F, Wang Y, Luo X, et al. Anti-CD24 Antibody-nitric oxide conjugate selectively and potently suppresses hepatic carcinoma. Cancer Research 2019;79:3395-405.

95. Wang L, Su W, Liu Z, et al. CD44 antibody-targeted liposomal nanoparticles for molecular imaging and therapy of hepatocellular carcinoma. Biomaterials 2012;33:5107-14.

96. Lee J, Gordon AC, Kim H, et al. Targeted multimodal nano-reporters for pre-procedural MRI and intra-operative image-guidance. Biomaterials 2016;109:69-77.

97. Yang R, An LY, Miao QF, et al. Effective elimination of liver cancer stem-like cells by CD90 antibody targeted thermosensitive magnetoliposomes. Oncotarget 2016;7:35894-916.

98. An Y, Yang R, Wang X, et al. Facile Assembly of thermosensitive liposomes for active targeting imaging and synergetic chemo-/magnetic hyperthermia therapy. Front Bioeng Biotechnol 2021;9:691091.

99. Han Y, An Y, Jia G, et al. Theranostic micelles based on upconversion nanoparticles for dual-modality imaging and photodynamic therapy in hepatocellular carcinoma. Nanoscale 2018;10:6511-23.

100. Vivier E, Raulet DH, Moretta A, et al. Innate or adaptive immunity? Science 2011;331:44-9.

101. Ames E, Canter RJ, Grossenbacher SK, et al. NK Cells preferentially target tumor cells with a cancer stem cell phenotype. J Immunol 2015;195:4010-9.

102. Han Y, Sun F, Zhang X, et al. CD24 targeting bi-specific antibody that simultaneously stimulates NKG2D enhances the efficacy of cancer immunotherapy. J Cancer Res Clin Oncol 2019;145:1179-90.

103. Yu M, Li Z. Natural killer cells in hepatocellular carcinoma: current status and perspectives for future immunotherapeutic approaches. Front Med 2017;11:509-21.

104. Chang YH, Connolly J, Shimasaki N, Mimura K, Kono K, Campana D. A chimeric receptor with NKG2D specificity enhances natural killer cell activation and killing of tumor cells. Cancer Res 2013;73:1777-86.

105. Kamiya T, Chang YH, Campana D. Expanded and activated natural killer cells for immunotherapy of hepatocellular carcinoma. Cancer Immunol Res 2016;4:574-81.

106. Lu SJ, Feng Q. CAR-NK cells from engineered pluripotent stem cells: Off-the-shelf therapeutics for all patients. Stem Cells Transl Med 2021;10 Suppl 2:S10-7.

107. Wrona E, Borowiec M, Potemski P. CAR-NK cells in the treatment of solid tumors. Int J Mol Sci 2021;22:5899.

108. Calderaro J, Rousseau B, Amaddeo G, et al. Programmed death ligand 1 expression in hepatocellular carcinoma: relationship with clinical and pathological features. Hepatology 2016;64:2038-46.

109. Hsu JM, Xia W, Hsu YH, et al. STT3-dependent PD-L1 accumulation on cancer stem cells promotes immune evasion. Nat Commun 2018;9:1908.

110. 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.

111. Finn RS, Ryoo B, Merle P, et al. for the KEYNOTE-240 Investigators. Results of KEYNOTE-240: phase 3 study of pembrolizumab (Pembro) vs best supportive care (BSC) for second line therapy in advanced hepatocellular carcinoma (HCC). JCO 2019;37:4004-4004.

112. Yau T, Park J, Finn R, et al. CheckMate 459: a randomized, multi-center phase III study of nivolumab (NIVO) vs sorafenib (SOR) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC). Ann Oncol 2019;30:v874-5.

113. Nishida N, Kudo M. Immune phenotype and immune checkpoint inhibitors for the treatment of human hepatocellular carcinoma. Cancers (Basel) 2020;12:1274.

114. Finn RS, Qin S, Ikeda M, et al. IMbrave150: updated overall survival (OS) data from a global, randomized, open-label phase III study of atezolizumab (atezo) + bevacizumab (bev) versus sorafenib (sor) in patients (pts) with unresectable hepatocellular carcinoma (HCC). JCO 2021;39:267-267.

115. Zhu AX, Finn RS, Ikeda M, et al. A phase Ib study of lenvatinib (LEN) plus pembrolizumab (PEMBRO) in unresectable hepatocellular carcinoma (uHCC). JCO 2020;38:4519-4519.

116. Ren Z, Xu J, Bai Y, et al. ORIENT-32 study group. Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study. Lancet Oncol 2021;22:977-90.

117. Xu J, Shen J, Gu S, et al. Camrelizumab in combination with apatinib in patients with advanced hepatocellular carcinoma (RESCUE): a nonrandomized, open-label, Phase II trial. Clin Cancer Res 2021;27:1003-11.

118. Zhang Y, Xu J, Shen J, et al. Update on overall survival (OS) of RESCUE: an open-label, phase 2 trial of camrelizumab (C) in combination with apatinib (A) in patients with advanced hepatocellular carcinoma (HCC). JCO 2021;39:4076-4076.

119. Parsa AT, Waldron JS, Panner A, et al. Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nat Med 2007;13:84-8.

120. Chen D, Li Z, Cheng Q, et al. Genetic alterations and expression of PTEN and its relationship with cancer stem cell markers to investigate pathogenesis and to evaluate prognosis in hepatocellular carcinoma. J Clin Pathol 2019;72:588-96.

121. Zhou H, Yu C, Kong L, et al. B591, a novel specific pan-PI3K inhibitor, preferentially targets cancer stem cells. Oncogene 2019;38:3371-86.

122. Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med 2018;378:439-48.

123. Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-Cell therapy in refractory large B-cell lymphoma. N Engl J Med 2017;377:2531-44.

124. Hegde PS, Chen DS. Top 10 challenges in cancer immunotherapy. Immunity 2020;52:17-35.

125. Wang H, Ye X, Ju Y, et al. Minicircle DNA-mediated CAR T cells targeting CD44 suppressed hepatocellular carcinoma both in vitro and in vivo. Onco Targets Ther 2020;13:3703-16.

126. Sun B, Yang D, Dai H, et al. Eradication Of Hepatocellular Carcinoma by NKG2D-Based CAR-T cells. Cancer Immunol Res 2019;7:1813-23.

127. Wang Y, Chen M, Wu Z, et al. CD133-directed CAR T cells for advanced metastasis malignancies: A phase I trial. Oncoimmunology 2018;7:e1440169.

128. Adusumilli PS, Zauderer MG, Rivière I, et al. A Phase I trial of regional mesothelin-targeted cAR T-cell therapy in patients with malignant pleural disease, in combination with the anti-PD-1 agent pembrolizumab. Cancer Discov 2021;11:2748-63.

129. Davies JS, Karimipour F, Zhang L, et al. Non-synergy of PD-1 blockade with T-cell therapy in solid tumors. J Immunother Cancer 2022;10:e004906.

130. Zhai B, Shi D, Gao H, et al. A phase I study of anti-GPC3 chimeric antigen receptor modified T cells (GPC3 CAR-T) in Chinese patients with refractory or relapsed GPC3+ hepatocellular carcinoma (r/r GPC3+ HCC). JCO 2017;35:3049-3049.

131. Batra SA, Rathi P, Guo L, et al. Glypican-3-specific CAR T cells coexpressing IL15 and IL21 have superior expansion and antitumor activity against hepatocellular carcinoma. Cancer Immunol Res 2020;8:309-20.

132. Pang N, Shi J, Qin L, et al. IL-7 and CCL19-secreting CAR-T cell therapy for tumors with positive glypican-3 or mesothelin. J Hematol Oncol 2021;14:118.

133. Adachi K, Kano Y, Nagai T, Okuyama N, Sakoda Y, Tamada K. IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor. Nat Biotechnol 2018;36:346-51.

134. Liang Z, Wu B, Ji Z, et al. The binding of LDN193189 to CD133 C-terminus suppresses the tumorigenesis and immune escape of liver tumor-initiating cells. Cancer Lett 2021;513:90-100.

135. Yu L, Yang X, Huang N, et al. A novel targeted GPC3/CD3 bispecific antibody for the treatment hepatocellular carcinoma. Cancer Biol Ther 2020;21:597-603.

136. Zhang P, Shi B, Gao H, et al. An EpCAM/CD3 bispecific antibody efficiently eliminates hepatocellular carcinoma cells with limited galectin-1 expression. Cancer Immunol Immunother 2014;63:121-32.

137. Burges A, Wimberger P, Kümper C, et al. Effective relief of malignant ascites in patients with advanced ovarian cancer by a trifunctional anti-EpCAM x anti-CD3 antibody: a phase I/II study. Clin Cancer Res 2007;13:3899-905.

138. Heiss MM, Murawa P, Koralewski P, et al. The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: Results of a prospective randomized phase II/III trial. Int J Cancer 2010;127:2209-21.

139. Wimberger P, Gilet H, Gonschior AK, et al. Deterioration in quality of life (QoL) in patients with malignant ascites: results from a phase II/III study comparing paracentesis plus catumaxomab with paracentesis alone. Ann Oncol 2012;23:1979-85.

140. Wierecky J, Mueller M, Brossart P. Dendritic cell-based cancer immunotherapy targeting MUC-1. Cancer Immunol Immunother 2006;55:63-7.

141. Sun JC, Pan K, Chen MS, et al. Dendritic cells-mediated CTLs targeting hepatocellular carcinoma stem cells. Cancer Biol Ther 2010;10:368-75.

142. Choi YJ, Park SJ, Park YS, Park HS, Yang KM, Heo K. EpCAM peptide-primed dendritic cell vaccination confers significant anti-tumor immunity in hepatocellular carcinoma cells. PLoS One 2018;13:e0190638.

143. Pang YB, He J, Cui BY, et al. A potential antitumor effect of dendritic cells fused with cancer stem cells in hepatocellular carcinoma. Stem Cells Int 2019;2019:5680327.

144. Yang Y, Hou J, Lin Z, et al. Attenuated Listeria monocytogenes as a cancer vaccine vector for the delivery of CD24, a biomarker for hepatic cancer stem cells. Cell Mol Immunol 2014;11:184-96.

145. Héninger E, Krueger TE, Lang JM. Augmenting antitumor immune responses with epigenetic modifying agents. Front Immunol 2015;6:29.

146. 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.

147. Woller N, Gürlevik E, Fleischmann-Mundt b, et al. viral infection of tumors overcomes resistance to PD-1-immunotherapy by broadening neoantigenome-directed T-cell responses. Mol Ther 2015;23:1630-40.

148. Shigeta K, Datta M, Hato T, et al. Dual programmed death receptor-1 and vascular endothelial growth factor receptor-2 blockade promotes vascular normalization and enhances antitumor immune responses in hepatocellular carcinoma. Hepatology 2020;71:1247-61.

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https://www.portico.org/publishers/oae/

Portico

All published articles are preserved here permanently:

https://www.portico.org/publishers/oae/