Natural Killer Cells and Regulatory T Cells Cross Talk in Hepatocellular Carcinoma: Exploring Therapeutic Options for the Next Decade

被引:38
作者
Bozward, Amber G. [1 ,2 ,3 ]
Warricker, Frazer [4 ,5 ]
Oo, Ye H. [1 ,2 ,3 ,6 ]
Khakoo, Salim, I [4 ,5 ,6 ]
机构
[1] Univ Birmingham, Ctr Liver & Gastroenterol Res, Inst Immunol & Immunotherapy, Biomed Res Ctr NIHR BRC Birmingham, Birmingham, W Midlands, England
[2] Univ Birmingham, Natl Inst Hlth Res, Inst Immunol & Immunotherapy, Biomed Res Ctr NIHR BRC Birmingham, Birmingham, W Midlands, England
[3] European Reference Network Ctr Rare Liver, Ctr Rare Dis, Birmingham, W Midlands, England
[4] Univ Southampton, Fac Med, Sch Clin & Expt Sci, Southampton, Hants, England
[5] Univ Southampton, NIHR Biomed Res Ctr, Sch Clin & Expt Sci, Southampton, Hants, England
[6] Univ Hosp Birmingham NHS Fdn Trust, Liver Transplant & Hepatobiliary Unit, Birmingham, W Midlands, England
来源
FRONTIERS IN IMMUNOLOGY | 2021年 / 12卷
基金
英国医学研究理事会;
关键词
liver; NK cells; regulatory T cells; hepatocellular carcinoma; tumour microenvironment; GMP cell therapy; NK CELLS; SURVIVAL; IMMUNOTHERAPY; EXPRESSION; RECEPTORS; LANDSCAPE; CTLA-4; TIGIT;
D O I
10.3389/fimmu.2021.643310
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Despite major advances in immunotherapy, hepatocellular carcinoma (HCC) remains a challenging target. Natural Killer (NK) cells are crucial components of the anti-HCC immune response, which can be manipulated for immunotherapeutic benefit as primary targets, modulators of the tumour microenvironment and in synchronising with tumour antigen specific effector CD8 cells for tumour clearance. Regulatory T cells shape the anti-tumour response from effector T cells via multiple suppressive mechanisms. Future research is needed to address the development of novel NK cell-targeted immunotherapy and on restraining Treg frequency and function in HCC. We have now entered a new era of anti-cancer treatment using checkpoint inhibitor (CPI)-based strategies. Combining GMP-NK cell immunotherapy to enhance the frequency of NK cells with CPI targeting both NK and CD8 T cells to release co-inhibitory receptors and enhance the cells anti-tumour immunity of HCC would be an attractive therapeutic option in the treatment of HCC. These therapeutic approaches should now be complemented by the application of genomic, proteomic and metabolomic approaches to understanding the microenvironment of HCC which, together with deep immune profiling of peripheral blood and HCC tissue before and during treatment, will provide the much-needed personalised medicine approach required to improve clinical outcomes for patients with HCC.
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页数:17
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