Abstract：Hepatocellular carcinoma (HCC), as the most common type of primary liver cancer, leads to heavy economic and health burdens to patients. With the progress of immunology research about HCC, the role of memory CD8+ T cells in HCC suppression is gradually recognized. This article reviewes exogenous and endogenous immunotherapy based on the specific distribution, surface molecules, and functions of memory CD8+ T cells subsets. The exogenous immunotherapy mainly contains adoptive immunotherapy carried by memory CD8+ T cells, while the endogenous mainly contains targeted therapies targeting immunosuppressive molecules. Memory CD8+ T cell-associated immunotherapy has shown good efficacy in both animal and human trials in HCC, and it is hopeful for a bright future to the treatment of HCC.
[1] Bray F，Ferlay J，Soerjomataram I，et al. Global cancer statistics 2018： GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin，2018，68（6）：394-424.
[2] 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 [J]. Hepatology（Baltimore，Md.），2018，68（2）：723-750.
[3] Ringelhan M，Pfister D，O’Connor T，et al. The immunology of hepatocellular carcinoma [J]. Nat Immunol，2018，19（3）：222-232.
[4] Garnelo M，Tan A，Her Z，et al. Interaction between tumour-infiltrating B cells and T cells controls the progression of hepatocellular carcinoma [J]. Gut，2017，66（2）：342-351.
[5] Han J，Khatwani N，Searles TG，et al. Memory CD8+ T cell responses to cancer [J]. Semin Immunol，2020，49：101435.
[6] Chaoul N，Mancarella S，Lupo L，et al. Impaired Anti-Tumor T cell Response in Hepatocellular Carcinoma [J]. Cancers （Basel），2020，12（3）：16-25.
[7] Chew V，Lai L，Pan L，et al. Delineation of an immunosuppressive gradient in hepatocellular carcinoma using high-dimensional proteomic and transcriptomic analyses [J]. Proc Natl Acad Sci U S A，2017，114（29）：e5900-e5909.
[8] Gao Q，Zhou J，Wang XY，et al. Infiltrating memory/senescent T cell ratio predicts extrahepatic metastasis of hepatocellular carcinoma [J]. Ann Surg Oncol，2012，19（2）：455-466.
[9] Turner SJ，Bennett TJ，La Gruta NL. CD8+ T-Cell Memory：The Why，the When，and the How [J]. Cold Spring Harb Perspect Biol，2021，13（5）：a038661.
[10] Parga-Vidal L，van Gisbergen KPJM. Area under Immunosurveillance：Dedicated Roles of Memory CD8 T-Cell Subsets [J]. Cold Spring Harbor perspectives in biology，2020，12（11）：a037796.
[11] Xu L，Zhang Y，Luo G，et al. The roles of stem cell memory T cells in hematological malignancies [J]. J Hematol Oncol，2015，8：113.
[12] Liu Q，Sun Z，Chen L. Memory T cells：strategies for optimizing tumor immunotherapy [J]. Protein Cell，2020，11（8）：549-564.
[13] Park SL，Zaid A，Hor JL，et al. Local proliferation maintains a stable pool of tissue-resident memory T cells after antiviral recall responses [J]. Nature immunology，2018， 19（2）： 183-191.
[14] Henson SM，Riddell NE，Akbar AN. Properties of end-stage human T cells defined by CD45RA re-expression [J]. Curr Opin Immunol，2012，24（4）：476-481.
[15] Klebanoff CA，Gattinoni L，Torabi-Parizi P，et al. Central memory self/tumor-reactive CD8+ T cells confer superior antitumor immunity compared with effector memory T cells [J]. Proc Natl Acad Sci U S A，2005，102（27）：9571-9576.
[16] Klebanoff CA，Gattinoni L，Palmer DC，et al. Determinants of successful CD8+ T-cell adoptive immunotherapy for large established tumors in mice [J]. Clin Cancer Res，2011，17（16）：5343-5352.
[17] Shimizu Y，Watanabe A，Whiteside TL. Memory T-lymphocytes are the main population of tumor-infiltrating lymphocytes obtained from human primary liver tumors [J]. J Hepatol，1992，16（1/2）：197-202.
[18] Di Blasi D，Boldanova T，Mori L，et al. Unique T-Cell Populations Define Immune-Inflamed Hepatocellular Carcinoma [J]. Cell Mol Gastroenterol Hepatol，2020，9（2）：195-218.
[19] Brunner SM，Rubner C，Kesselring R，et al. Tumor-infiltrating，interleukin-33-producing effector-memory CD8+ T cells in resected hepatocellular carcinoma prolong patient survival [J]. Hepatology，2015，61（6）：1957-1967.
[20] Duan M，Goswami S，Shi JY，et al. Activated and Exhausted MAIT Cells Foster Disease Progression and Indicate Poor Outcome in Hepatocellular Carcinoma [J]. Clin Cancer Res，2019，25（11）：3304-3316.
[21] Fonseca R，Beura LK，Quarnstrom CF，et al. Developmental plasticity allows outside-in immune responses by resident memory T cells [J]. Nat Immunol，2020，21（4）：412-421.
[22] Pallett LJ，Burton AR，Amin OE，et al. Longevity and replenishment of human liver-resident memory T cells and mononuclear phagocytes [J]. J Exp Med，2020，217（9）：1-9.
[23] Zhu W，Peng Y，Wang L，et al. Identification of α-fetoprotein-specific T-cell receptors for hepatocellular carcinoma immunotherapy [J]. Hepatology，2018，68（2）：574-589.
[24] Tan AT，Yang N，Lee Krishnamoorthy T，et al. Use of Expression Profiles of HBV-DNA Integrated Into Genomes of Hepatocellular Carcinoma Cells to Select T Cells for Immunotherapy [J]. Gastroenterology，2019，156（6）：1862-1876.e9.
[25] Berger C，Jensen MC，Lansdorp PM，et al. Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primates [J]. J Clin Invest，2008，118（1）：294-305.
[26] Oliveira G，Ruggiero E，Stanghellini MT，et al. Tracking genetically engineered lymphocytes long-term reveals the dynamics of T cell immunological memory [J]. Sci Transl Med，2015，7（317）：317ra198.
[27] Chen Y，E CY，Gong ZW，et al. Chimeric antigen receptor-engineered T-cell therapy for liver cancer [J]. Hepatobiliary Pancreat Dis Int，2018，17（4）：301-309.
[28] Zhang L，Ding J，Li HY，et al. Immunotherapy for advanced hepatocellular carcinoma，where are we? [J]. Biochim Biophys Acta Rev Cancer，2020，1874（2）：188441.
[29] Xu Y，Zhang M，Ramos CA，et al. Closely related T-memory stem cells correlate with in vivo expansion of CAR.CD19-T cells and are preserved by IL-7 and IL-15 [J]. Blood，2014，123（24） 3750-3759.
[30] Huang W，Liu Y，Hu Y，et al. Construction and function of Glypican-3-targeted fourth-generation chimeric antigen receptor T cells （secreting IL-7 and CCL19） [J]. Sheng Wu Gong Cheng Xue Bao，2020，36（5）：979-991.
[31] 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 [J]. Gastroenterology，2020，159（2）：609-623.
[32] Sheng H，Huang Y，Xiao Y，et al. ATR inhibitor AZD6738 enhances the antitumor activity of radiotherapy and immune checkpoint inhibitors by potentiating the tumor immune microenvironment in hepatocellular carcinoma [J]. J Immunother Cancer，2020，8（1）：37-45.
[33] Yang W，Feng Y，Zhou J，et al. A selective HDAC8 inhibitor potentiates antitumor immunity and efficacy of immune checkpoint blockade in hepatocellular carcinoma [J]. Sci Transl Med，2021，13（588）：116-127.
[34] Qi X，Yang M，Ma L，et al. Synergizing sunitinib and radiofrequency ablation to treat hepatocellular cancer by triggering the antitumor immune response [J]. J Immunother Cancer，2020，8（2）：25-36.
[35] Han Q，Wang Y，Pang M，et al. STAT3-blocked whole-cell hepatoma vaccine induces cellular and humoral immune response against HCC [J]. J Exp Clin Cancer Res，2017，36（1）：156.
[36] Hong Y，Peng Y，Guo ZS，et al. Epitope-optimized alpha-fetoprotein genetic vaccines prevent carcinogen-induced murine autochthonous hepatocellular carcinoma [J]. Hepatology，2014，59（4）：1448-1458.
[37] Han JW，Yoon SK. Tissue-Resident Lymphocytes：Implications in Immunotherapy for Hepatocellular Carcinoma [J]. Int J Mol Sci，2020，22（1）：232.
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