Emerging potential of CAR-NK cell therapy for hepatocellular carcinoma: current advances and translational challenges

Abstract

Chimeric antigen receptor-natural killer (CAR-NK) therapy represents an emerging new direction in fighting against cancer. In recent years, it has attracted significant attention, largely due to its notable safety advantages over CAR-T cell therapy and its potential for reduced side effects. In this article, we will review the recent preclinical advances and translational challenges in CAR-NK therapy for the treatment of hepatocellular carcinoma (HCC). Several preclinical studies have successfully demonstrated that targeting HCC-associated tumor antigens such as glypican-3 and cluster of differentiation 147 (CD147) could exert a strong anti-tumor efficacy. However, only a few studies have entered the clinical stage, with none having progressed to late-phase trials. The clinical translation of CAR-NK in HCC is mainly hindered by significant challenges, including the immunosuppressive tumor microenvironment, inefficient tumor trafficking, tumor heterogeneity, and poor persistence of infused cells. To overcome these barriers, researchers have been exploring different innovative strategies such as disrupting the transforming growth factor-β signaling, engineering homing chemokine receptors, developing multi-specific CARs, and enhancing persistence with cytokine support (e.g., interleukin-15). Further ongoing research is important to optimize the CAR constructs and identify effective combination approaches to enhance the overall treatment efficacy.

Keywords

Chimeric antigen receptor technology / liver cancer therapy / cell-based immunotherapy

References

[1] International Agency for Research on Cancer, World Health Organization. Liver and intrahepatic bile ducts fact sheet. Available from: https://gco.iarc.who.int/media/globocan/factsheets/cancers/11-liver-and-intrahepatic-bile-ducts-fact-sheet.pdf. [Last accessed on 5 Jan 2026]

[2] Rumgay H,de Martel C.Global, regional and national burden of primary liver cancer by subtype.Eur J Cancer2022;161:108-18

[3] Singh SP,Chand P.Global epidemiology of hepatocellular carcinoma.J Clin Exp Hepatol2025;15:102446

[4] Llovet JM,Pikarsky E.Hepatocellular carcinoma.Nat Rev Dis Primers2016;2:16018

[5] Tabori NE.Treatment options for early-stage hepatocellular carcinoma.Semin Intervent Radiol2020;37:448-55 PMCID:PMC7732557

[6] Podlasek A,Broering D.Recent advances in locoregional therapy of hepatocellular carcinoma.Cancers2023;15:3347 PMCID:PMC10341377

[7] Liu L,Chen C.Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5.Cancer Res2006;66:11851-8

[8] Matsuki M,Yamamoto Y.Lenvatinib inhibits angiogenesis and tumor fibroblast growth factor signaling pathways in human hepatocellular carcinoma models.Cancer Med2018;7:2641-53 PMCID:PMC6010799

[9] Kissel M,Fiebig L.Antitumor effects of regorafenib and sorafenib in preclinical models of hepatocellular carcinoma.Oncotarget2017;8:107096-108 PMCID:PMC5739799

[10] Li Q,Yang Y.PD-1/PD-L1 checkpoint inhibitors in advanced hepatocellular carcinoma immunotherapy.Front Immunol2022;13:1070961 PMCID:PMC9806143

[11] Gaudel P,Fields-Meehan J.Nivolumab use for first-line management of hepatocellular carcinoma: results of a real-world cohort of patients.Fed Pract2021;38:89-91 PMCID:PMC7953859

[12] El-Khoueiry AB,Yau T.Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial.Lancet2017;389:2492-502 PMCID:PMC7539326

[13] Melero I,Kang YK.Nivolumab plus ipilimumab combination therapy in patients with advanced hepatocellular carcinoma previously treated with sorafenib: 5-year results from CheckMate 040.Ann Oncol2024;35:537-48

[14] Zugasti I,Fidyt K.CAR-T cell therapy for cancer: current challenges and future directions.Signal Transduct Target Ther2025;10:210 PMCID:PMC12229403

[15] Chen S,Jounaidi Y.Comprehensive snapshots of natural killer cells functions, signaling, molecular mechanisms and clinical utilization.Signal Transduct Target Ther2024;9:302 PMCID:PMC11544004

[16] Nagler A,Cwirla S.Comparative studies of human FcRIII-positive and negative natural killer cells.J Immunol1989;143:3183-91

[17] Mandelboim O,Davis DM,Boyson JE.Human CD16 as a lysis receptor mediating direct natural killer cell cytotoxicity.Proc Natl Acad Sci U S A1999;96:5640-4 PMCID:PMC21913

[18] Kärre K,Piontek G.Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy.Nature1986;319:675-8

[19] Bern MD,Yang L,Poursine-Laurent J.Inducible down-regulation of MHC class I results in natural killer cell tolerance.J Exp Med2019;216:99-116 PMCID:PMC6314522

[20] Kamiya T,Wong D,Campana D.Blocking expression of inhibitory receptor NKG2A overcomes tumor resistance to NK cells.J Clin Invest2019;129:2094-106 PMCID:PMC6486333

[21] Xue TY,Zhang JJ.KIR2DL1-HLA signaling pathway: notable inhibition in the cytotoxicity of allo-NK cell against KG1A cell.Clin Lab2013;59:613-9

[22] Sun H,Huang M.Human CD96 correlates to natural killer cell exhaustion and predicts the prognosis of human hepatocellular carcinoma.Hepatology2019;70:168-83

[23] Yu Y.The function of NK cells in tumor metastasis and NK cell-based immunotherapy.Cancers2023;15:2323 PMCID:PMC10136863

[24] Bauer S,Wu J.Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA.Science1999;285:727-9

[25] Sivori S,Bottino C.NKp46 is the major triggering receptor involved in the natural cytotoxicity of fresh or cultured human NK cells. Correlation between surface density of NKp46 and natural cytotoxicity against autologous, allogeneic or xenogeneic target cells.Eur J Immunol1999;29:1656-66

[26] Pende D,Pessino A.Identification and molecular characterization of NKp30, a novel triggering receptor involved in natural cytotoxicity mediated by human natural killer cells.J Exp Med1999;190:1505-16 PMCID:PMC2195691

[27] Wang R,Stutzman NC,Sun PD.Natural killer cell-produced IFN-γ and TNF-α induce target cell cytolysis through up-regulation of ICAM-1.J Leukoc Biol2012;91:299-309 PMCID:PMC3290424

[28] Gauthier L,Anceriz N.Multifunctional natural killer cell engagers targeting NKp46 trigger protective tumor immunity.Cell2019;177:1701-1713.e16

[29] Parums DV.A review of CAR T cells and adoptive T-cell therapies in lymphoid and solid organ malignancies.Med Sci Monit2025;31:e948125 PMCID:PMC11800685

[30] Frey N.Cytokine release syndrome with chimeric antigen receptor T cell therapy.Biol Blood Marrow Transplant2019;25:e123-7

[31] Shimabukuro-Vornhagen A,Subklewe M.Cytokine release syndrome.J Immunother Cancer2018;6:56 PMCID:PMC6003181

[32] Giavridis T,Eyquem J,Piersigilli A.CAR T cell-induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade.Nat Med2018;24:731-8 PMCID:PMC6410714

[33] Cao JX,Gao WJ,Wu LH.The incidence of cytokine release syndrome and neurotoxicity of CD19 chimeric antigen receptor-T cell therapy in the patient with acute lymphoblastic leukemia and lymphoma.Cytotherapy2020;22:214-26

[34] Sterner RC.Immune effector cell associated neurotoxicity syndrome in chimeric antigen receptor-T cell therapy.Front Immunol2022;13:879608 PMCID:PMC9445841

[35] Ursu R,Cuzzubbo S.CAR T-cell-associated neurotoxicity: a comprehensive review.Rev Neurol2024;180:989-94

[36] Balkhi S,Di Spirito A,Mortara L.CAR-NK cell therapy: promise and challenges in solid tumors.Front Immunol2025;16:1574742 PMCID:PMC12009813

[37] Liu E,Banerjee P.Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors.N Engl J Med2020;382:545-53 PMCID:PMC7101242

[38] Gong JH,Klingemann HG.Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells.Leukemia1994;8:652-8

[39] Liu Q,Mou J.Irradiated chimeric antigen receptor engineered NK-92MI cells show effective cytotoxicity against CD19⁺ malignancy in a mouse model.Cytotherapy2020;22:552-62

[40] Klingemann H,Toneguzzo F.Natural Killer Cells for Immunotherapy - advantages of the NK-92 Cell Line over Blood NK Cells.Front Immunol2016;7:91 PMCID:PMC4789404

[41] Zotto G, Antonini F, Pesce S, Moretta F, Moretta L, Marcenaro E. Comprehensive phenotyping of human PB NK cells by flow cytometry.Cytometry A2020;97:891-9

[42] Ruggeri L,Urbani E.Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants.Science2002;295:2097-100

[43] Woll PS,Tian X.Human embryonic stem cells differentiate into a homogeneous population of natural killer cells with potent in vivo antitumor activity.Blood2009;113:6094-101 PMCID:PMC2699231

[44] Takahashi K.Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.Cell2006;126:663-76

[45] Zhao J,Sun C,Yang XM.Induced pluripotent stem cells: origins, applications, and future perspectives.J Zhejiang Univ Sci B2013;14:1059-69 PMCID:PMC3863365

[46] Cichocki F,Gaidarova S.iPSC-derived NK cells maintain high cytotoxicity and enhance in vivo tumor control in concert with T cells and anti-PD-1 therapy.Sci Transl Med2020;12 PMCID:PMC8861807

[47] Elahi R,Hadiloo K.Chimeric antigen receptor-engineered natural killer (CAR NK) cells in cancer treatment; recent advances and future prospects.Stem Cell Rev Rep2021;17:2081-106 PMCID:PMC8410173

[48] Alabanza L,Geldres C.Function of novel anti-CD19 chimeric antigen receptors with human variable regions is affected by hinge and transmembrane domains.Mol Ther2017;25:2452-65 PMCID:PMC5675490

[49] Hudecek M,Kosasih PL.The nonsignaling extracellular spacer domain of chimeric antigen receptors is decisive for in vivo antitumor activity.Cancer Immunol Res2015;3:125-35 PMCID:PMC4692801

[50] Pinto E,Compagnone M.From ex vivo to in vivo chimeric antigen T cells manufacturing: new horizons for CAR T-cell based therapy.J Transl Med2025;23:10 PMCID:PMC11700462

[51] Tousley AM,Labanieh L.Co-opting signalling molecules enables logic-gated control of CAR T cells.Nature2023;615:507-16 PMCID:PMC10564584

[52] der Stegen SJ, Hamieh M, Sadelain M. The pharmacology of second-generation chimeric antigen receptors.Nat Rev Drug Discov2015;14:499-509 PMCID:PMC6410718

[53] Cook MS,Flaherty KR.CAR-T cells containing CD28 versus 4-1BB co-stimulatory domains show distinct metabolic profiles in patients.Cell Rep2025;44:115973

[54] Zhong XS,Plotkin J,Sadelain M.Chimeric antigen receptors combining 4-1BB and CD28 signaling domains augment PI₃kinase/AKT/Bcl-X_L activation and CD8⁺ T cell-mediated tumor eradication.Mol Ther2010;18:413-20 PMCID:PMC2839303

[55] Guedan S,Shaw C.Enhancing CAR T cell persistence through ICOS and 4-1BB costimulation.JCI Insight2018;3:96976 PMCID:PMC5821198

[56] Long AH,Shern JF.4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors.Nat Med2015;21:581-90 PMCID:PMC4458184

[57] Chmielewski M.TRUCKs: the fourth generation of CARs.Expert Opin Biol Ther2015;15:1145-54

[58] Yeku OO,Koneru M,Brentjens RJ.Armored CAR T cells enhance antitumor efficacy and overcome the tumor microenvironment.Sci Rep2017;7:10541 PMCID:PMC5585170

[59] Pegram HJ,Hayman EG.Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning.Blood2012;119:4133-41 PMCID:PMC3359735

[60] Kagoya Y,Guo T.A novel chimeric antigen receptor containing a JAK-STAT signaling domain mediates superior antitumor effects.Nat Med2018;24:352-9 PMCID:PMC5839992

[61] Ayala MG,Hong E.Abstract 2905: SENTI-301A, an off-the-shelf multi-armed preclinical CAR-NK cell therapy, for the treatment of GPC3 expressing tumors.Cancer Res2023;83:2905-2905

[62] Kaveri D,Leitner E. SENTI-301A, an off-the-shelf multi-armed preclinical CAR-NK cell therapy for the treatment of GPC3 expressing tumors. American Association for Cancer Research. Available from: https://www.sentibio.com/wp-content/uploads/2023/12/SENTI-301A_AACR_2023_Poster_SentiBio_EH_FINAL.pdf. [Last accessed on 5 Jan 2026]

[63] National Center for Biotechnology Information, National Institutes of Health. Clinical Study of SN301A injection in the Treatment of hepatocellular Carcinoma (SN301A). Available from: https://clinicaltrials.gov/study/NCT06652243. [Last accessed on 5 Jan 2026]

[64] National Center for Biotechnology Information, National Institutes of Health. CAR-pNK cell immunotherapy in MUC1 Positive relapsed or refractory solid tumor. Available from: https://clinicaltrials.gov/study/NCT02839954. [Last accessed on 5 Jan 2026]

[65] National Center for Biotechnology Information, National Institutes of Health. Single-arm, open-label clinical study of SZ003 in the treatment of advanced hepatocellular carcinoma. Available from: https://clinicaltrials.gov/study/NCT05845502. [Last accessed on 5 Jan 2026]

[66] Cao B,Chen Z.Development of glypican-3-specific chimeric antigen receptor-modified natural killer cells and optimization as a therapy for hepatocellular carcinoma.J Leukoc Biol2025;117:qiae144

[67] Lin X,Dong X.Radiotherapy enhances the anti-tumor effect of CAR-NK cells for hepatocellular carcinoma.J Transl Med2024;22:929 PMCID:PMC11472550

[68] Chen L,Adah D.Soluble programmed death ligand-1-induced immunosuppressive effects on chimeric antigen receptor-natural killer cells targeting Glypican-3 in hepatocellular carcinoma.Immunology2023;169:204-18 PMCID:PMC10712665

[69] Thangaraj JL,Lopez E.Disruption of TGF-β signaling pathway is required to mediate effective killing of hepatocellular carcinoma by human iPSC-derived NK cells.Cell Stem Cell2024;31:1327-1343.e5 PMCID:PMC11380586

[70] Tseng HC,Badeti S.Efficacy of anti-CD147 chimeric antigen receptors targeting hepatocellular carcinoma.Nat Commun2020;11:4810 PMCID:PMC7511348

[71] Sabha Y,Tseng HC.CD147-CAR-NK cell therapy shows minimal toxicities in human CD147 transgenic mouse model with solid tumors.Mol Ther Oncol2025;33:200957 PMCID:PMC11952776

[72] Ma M,Byrne M.Evaluation of combination mTOR agonist and CD147-IL15-CAR-NK cell therapy in transgenic human CD147 hepatocellular carcinoma models.J Immunol2024;212:0771_4477

[73] Liu B,Zhou ML.Development of c‑MET‑specific chimeric antigen receptor‑engineered natural killer cells with cytotoxic effects on human liver cancer HepG2 cells.Mol Med Rep2019;20:2823-31 PMCID:PMC6691195

[74] Anderson NM.The tumor microenvironment.Curr Biol2020;30:R921-5 PMCID:PMC8194051

[75] Rodriguez PC,Ochoa AC.L-arginine availability regulates T-lymphocyte cell-cycle progression.Blood2007;109:1568-73 PMCID:PMC1794048

[76] Krishnamoorthy M,Maleki Vareki S.Immunosuppressive effects of myeloid-derived suppressor cells in cancer and immunotherapy.Cells2021;10:1170 PMCID:PMC8150533

[77] Hoechst B,Ormandy L.Myeloid derived suppressor cells inhibit natural killer cells in patients with hepatocellular carcinoma via the NKp30 receptor.Hepatology2009;50:799-807 PMCID:PMC6357774

[78] Wu Y,Pan WD.Monocyte/macrophage-elicited natural killer cell dysfunction in hepatocellular carcinoma is mediated by CD48/2B4 interactions.Hepatology2013;57:1107-16

[79] Li T,Hua X.Hepatocellular carcinoma-associated fibroblasts trigger NK cell dysfunction via PGE2 and IDO.Cancer Lett2012;318:154-61

[80] Jin X,Wang N.High expression of TGF-β1 contributes to hepatocellular carcinoma prognosis via regulating tumor immunity.Front Oncol2022;12:861601 PMCID:PMC9082360

[81] Liang S,Zuo B.SMAD7 expression in CAR-T cells improves persistence and safety for solid tumors.Cell Mol Immunol2024;21:213-26 PMCID:PMC10901810

[82] Yu J,Becknell B.Pro- and antiinflammatory cytokine signaling: reciprocal antagonism regulates interferon-gamma production by human natural killer cells.Immunity2006;24:575-90

[83] Castriconi R,Della Chiesa M.Transforming growth factor beta 1 inhibits expression of NKp30 and NKG2D receptors: consequences for the NK-mediated killing of dendritic cells.Proc Natl Acad Sci U S A2003;100:4120-5 PMCID:PMC153058

[84] Strati P,Majhail NS.Chimeric antigen receptor T-cell therapy for hematologic malignancies: a practical review.JCO Oncol Pract2023;19:706-13

[85] Bule P,Aires-Da-Silva F.Chemokine-directed tumor microenvironment modulation in cancer immunotherapy.Int J Mol Sci2021;22:9804 PMCID:PMC8464715

[86] Liu G,Zheng H.CXCR2-modified CAR-T cells have enhanced trafficking ability that improves treatment of hepatocellular carcinoma.Eur J Immunol2020;50:712-24

[87] El-Sayes N,Mossman K.Tumor heterogeneity: a great barrier in the age of cancer immunotherapy.Cancers2021;13:806 PMCID:PMC7918981

[88] Lu Y.Strategies to overcome tumour relapse caused by antigen escape after CAR T therapy.Mol Cancer2025;24:126 PMCID:PMC12036236

[89] Sun L,Gao Z.Shed antigen-induced blocking effect on CAR-T cells targeting glypican-3 in hepatocellular carcinoma.J Immunother Cancer2021;9:e001875 PMCID:PMC8039282

[90] Zhou L,Zheng D.Bispecific CAR-T cells targeting FAP and GPC3 have the potential to treat hepatocellular carcinoma.Mol Ther Oncol2024;32:200817 PMCID:PMC11179089

[91] Deng Y,Na J.Prospects and limitations of NK cell adoptive therapy in clinical applications.Cancer Metastasis Rev2025;44:57

[92] Liu E,Dotti G.Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity.Leukemia2018;32:520-31 PMCID:PMC6063081

[93] Conlon KC,Welles HC.Redistribution, hyperproliferation, activation of natural killer cells and CD8 T cells, and cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer.J Clin Oncol2015;33:74-82 PMCID:PMC4268254

[94] Li YR,Fang Y,Yang L.Emerging trends in clinical allogeneic CAR cell therapy.Med2025;6:100677

[95] Damodharan SN,Forsberg MH.Analysis of ex vivo expanded and activated clinical-grade human NK cells after cryopreservation.Cytotherapy2020;22:450-7 PMCID:PMC7387178

[96] Oyer JL,Dieffenthaller TA.Cryopreserved PM21-particle-expanded natural killer cells maintain cytotoxicity and effector functions in vitro and in vivo.Front Immunol2022;13:861681 PMCID:PMC9022621

[97] Mark C,Roessner S.Cryopreservation impairs 3-D migration and cytotoxicity of natural killer cells.Nat Commun2020;11:5224 PMCID:PMC7568558

[98] Min B,Her JH.Optimization of large-scale expansion and cryopreservation of human natural killer cells for anti-tumor therapy.Immune Netw2018;18:e31 PMCID:PMC6117513

[99] Otegbeye F,Caimi P.A phase I study to determine the maximum tolerated dose of ex vivo expanded natural killer cells derived from unrelated, HLA-disparate adult donors.Transplant Cell Ther2022;28:250.e1-8 PMCID:PMC9489303

[100] Litvinova Y,Allin S.Availability and financing of CAR-T cell therapies: a cross-country comparative analysis.Health Policy2024;149:105153

[101] Valeri A,Castellano E.Overcoming tumor resistance mechanisms in CAR-NK cell therapy.Front Immunol2022;13:953849 PMCID:PMC9381932

[102] Li YR,Niu S,Lyu Z.Managing allorejection in off-the-shelf CAR-engineered cell therapies.Mol Ther2025;33:2368-90 PMCID:PMC12172182

[103] Li X,Ou Y,Xu W.Optimizing treatment selection for early hepatocellular carcinoma based on tumor biology, liver function, and patient status.J Hepatocell Carcinoma2025;12:777-90 PMCID:PMC12009567

[104] Peng X,Zhang W.Advanced development of biomarkers for immunotherapy in hepatocellular carcinoma.Front Oncol2022;12:1091088 PMCID:PMC9885011

[105] Gu X,Zhou W.Infusion and delivery strategies to maximize the efficacy of CAR-T cell immunotherapy for cancers.Exp Hematol Oncol2024;13:70 PMCID:PMC11282638

[106] Fan J,Huang XW.Phase I study of Ori-C101, an armored GPC3-directed CAR-T, in patients with advanced hepatocellular carcinoma (HCC).J Clin Oncol2025;43:4084

[107] Turicek DP,Moraly J,Shah NN.CAR T-cell detection scoping review: an essential biomarker in critical need of standardization.J Immunother Cancer2023;11:e006596 PMCID:PMC10230989

[108] Shi D,Kaseb AO.Chimeric antigen receptor-glypican-3 T-cell therapy for advanced hepatocellular carcinoma: results of phase I trials.Clin Cancer Res2020;26:3979-89

[109] Galle PR,Kudo M.Biology and significance of alpha-fetoprotein in hepatocellular carcinoma.Liver Int2019;39:2214-29

[110] Liu F.The role of CD133 in hepatocellular carcinoma.Cancer Biol Ther2021;22:291-300 PMCID:PMC8183534

[111] Wang H,Ye X.Nonviral mcDNA-mediated bispecific CAR T cells kill tumor cells in an experimental mouse model of hepatocellular carcinoma.BMC Cancer2022;22:814 PMCID:PMC9310485

[112] Dai H,Shi D.Efficacy and biomarker analysis of CD133-directed CAR T cells in advanced hepatocellular carcinoma: a single-arm, open-label, phase II trial.Oncoimmunology2020;9:1846926 PMCID:PMC7714531

[113] Schneider D,Wu D.Trispecific CD19-CD20-CD22-targeting duoCAR-T cells eliminate antigen-heterogeneous B cell tumors in preclinical models.Sci Transl Med2021;13:eabc6401

[114] Zhao Y,Yang S.Bioorthogonal equipping CAR-T cells with hyaluronidase and checkpoint blocking antibody for enhanced solid tumor immunotherapy.ACS Cent Sci2022;8:603-14 PMCID:PMC9136969

[115] Miranda D,Ibañez J.PGC-1α-dependent mitochondrial adaptation is necessary to sustain IL-2-induced activities in human NK cells.Mediators Inflamm2016;2016:9605253 PMCID:PMC4931085

[116] Li X,Liu J.Dysregulation of the SREBP pathway is associated with poor prognosis and serves as a potential biomarker for the diagnosis of hepatocellular carcinoma.Mol Med Rep2025;31:1-14 PMCID:PMC11894594

[117] Assmann N,Donnelly RP.Srebp-controlled glucose metabolism is essential for NK cell functional responses.Nat Immunol2017;18:1197-206

[118] Han W,Wang M.Potential roles of serum exosomal CD155 and its impact on NK cell immunosuppression in hepatocellular carcinoma.Balkan Med J2025;42:242-53 PMCID:PMC12060579