PD-1抑制剂治疗肝细胞癌疗效相关生物标志物的研究现状

doi:10.11904/j.issn.1002-3070.2022.04.016

Abstract

Abstract: In recent years,immunotherapy has achieved preliminary results in the field of adjuvant therapy for liver cancer.Programmed cell death-1(PD-1)inhibitors are the current research hotspot,but the overall response rate is still not high.As expected,there is an urgent need to find suitable biomarkers to predict the efficacy of PD-1 inhibitors in the treatment for liver cancer patients.This article reviews the research progress of PD-1 inhibitor therapy related biomarkers for hepatocellular carcinoma.

Key words: PD-1 inhibitor, Hepatocellular carcinoma, Biomarkers

CLC Number:

R735.7

LIU Jia, YANG Daokun, WANG Yanping, CHEN Baoxin, WANG Xinwei, SHEN Jiao. Research status of biomarkers related to the efficacy of PD-1 inhibitors in the treatment of hepatocellular carcinoma[J]. Journal of Practical Oncology, 2022, 36(4): 374-380.

0
/ / Recommend

Add to citation manager EndNote|Reference Manager|ProCite|BibTeX|RefWorks

URL: http://journal09.magtechjournal.com/Jwk3_syzlxzz/EN/10.11904/j.issn.1002-3070.2022.04.016

http://journal09.magtechjournal.com/Jwk3_syzlxzz/EN/Y2022/V36/I4/374

References

1 Sung H,Ferlay J,Siegel RL,et al.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2021,71(3):209-249.
2 Tai D,Choo SP,Chew V.Rationale of immunotherapy in hepatocellular carcinoma and its potential biomarkers[J].Cancers(Basel),2019,11(12):1926.
3 Xu F,Jin T,Zhu Y,et al.Immune checkpoint therapy in liver cancer[J].Exp Clin Cancer Res,2018,37(1):110.
4 Petrella TM,Robert C,Richtig E,et al.Patient-reported outcomes in KEYNOTE-006,a randomised study of pembrolizumab versus ipilimumab in patients with advanced melanoma[J].Eur J Cancer,2017,86:115-124.
5 Feun LG,Li YY,Wu C,et al.Phase 2 study of pembrolizumab and circulating biomarkers to predict anticancer response in advanced,unresectable hepatoce llular carcinoma[J].Cancer,2019,125(20):3603-3614.
6 El-Khoueiry AB,Sangro B,Yau T,et al.Nivolumab in patients with advanced hepatocellular carcinoma(CheckMate 040):an open-label,non-comparative,phase 1/2 dose escalation and expansion trial[J].Lancet,2017,389(10088):2492-2502.
7 Liu CQ,Xu J,Zhou ZG,et al.Expression patterns of programmed death ligand 1 correlate with different microenvironments and patient prognosis in hepatoce llular carcinoma[J].Br J Cancer,2018,119(1):80-88.
8 Pinato DJ,Mauri FA,Spina P,et al.Clinical implications of heterogeneity in PD-L1 immunohistochemical detection in hepatocellular carcinoma:the Blueprint-HCC study[J].Br J Cancer,2019,120(11):1033-1036.
9 Galuppini F,Dal Pozzo CA,Deckert J,et al.Tumor mutation burden:from comprehensive mutational screening to the clinic[J].Cancer Cell Int,2019,19:209.
10 Jang BS,Han W,Kim IA.Tumor mutation burden,immune checkpoint crosstalk and radiosensitivity in single-cell RNA sequencing data of breast cancer[J].Radiother Oncol,2020,142:202-209.
11 Xu J,Zhang Y,Jia R,et al.Anti-PD-1 antibody SHR-1210 combined with apatinib for advanced hepatocellular carcinoma,gastric,or esophagogastric junction cancer:an open-label,dose escalation and expansion study[J].Clin Cancer Res,2019,25(2):515-523.
12 Huo J,Wu L,Zang Y.A Prognostic model of 15 immune-related gene Pairs associated with tumor mutation burden for hepatocellular carcinoma[J].Front Mol Biosci,2020,7:581354.
13 Li Z,Pearlman AH,Hsieh P.DNA mismatch repair and the DNA damage response[J].DNA Repair(Amst),2016,38:94-101.
14 Ang C,Klempner SJ,Ali SM,et al.Prevalence of established and emerging biomarkers of immune checkpoint inhibitor response in advanced hepatocellular carcinoma[J].Oncotarget,2019,10(40):4018-4025.
15 Meng L,Ma R,Yan R,et al.Profiles of immune infiltration in the tumor microenvironment of hepatocellular carcinoma[J].J Gastrointest Oncol,2021,12(3):1152-1163.
16 Zheng X,Jin W,Wang S,et al.Progression on the roles and mechanisms of tumor-infiltrating T lymphocytes in patients with hepatocellular carcinoma[J].Front Immunol,2021,12:729705.
17 Kaseb AO,Vence L,Blando J,et al.Immunologic correlates of pathologic complete response to preoperative immunotherapy in hepatocellular carcinoma[J].Cancer Immunol Res,2019,7(9):1390-1395.
18 Hsu CL,Ou DL,Bai LY,et al.Exploring markers of exhausted CD8 T cells to predict response to immune checkpoint inhibitor therapy for hepatocellular carcinoma[J].Liver Cancer,2021,10(4):346-359.
19 Siddiqui I,Schaeuble K,Chennupati V,et al.Intratumoral Tcf1+PD-1+ CD8⁺T Cells with stem-like properties promote tumor control in response to vac cination and checkpoint blockade immunotherapy[J].Immunity,2019,50(1):195-211.
20 Ng HHM,Lee RY,Goh S,et al.Immunohistochemical scoring of CD38 in the tumor microenvironment predicts responsiveness to anti-PD-1/PD-L1 immun otherapy in hepatocellular carcinoma[J].J Immunother Cancer,2020,8(2):987.
21 Ayers M,Lunceford J,Nebozhyn M,et al.IFN-γ-related mRNA profile predicts clinical response to PD-1 blockade[J].J Clin Invest,2017,127(8):2930-2940.
22 Brown ZJ,Fu Q,Ma C,et al.Carnitine palmitoyltransferase gene upregulation by linoleic acid induces CD4⁺T cell apoptosis promoting HCC development[J].Cell Death Dis,2018,9(6):620.
23 Lin SZ,Chen KJ,Xu ZY,et al.Prediction of recurrence and survival in hepatocellular carcinoma based on two Cox models mainly determined by FoxP3+ regulatory T cells[J].Cancer Prev Res(Phila),2013,6(6):594-602.
24 Ding W,Xu X,Qian Y,et al.Prognostic value of tumor-infiltrating lymphocyte in hepatocellular carcinoma:a meta-analysis[J].Medicine(Baltimore),2018,97(50):13301.
25 Kuang DM,Peng C,Zhao Q,et al.Activated monocytes in peritumoral stroma of hepatocellular carcinoma promote expansion of memory T helper 17 cells[J].Hepatology,2010,51(1):154-164.
26 Zhang H,Deng T,Liu R,et al.CAF secreted miR-522 suppresses ferroptosis and promotes acquired chemo-resistance in gastric cancer[J].Mol Cancer,2020,19(1):43.
27 Han Q,Zhao H,Jiang Y,et al.HCC-Derived Exosomes:critical player and target for cancer immune escape[J].Cells,2019,8(6):558.
28 Li X,Lei Y,Wu M,et al.Regulation of macrophage activation and polarization by HCC-derived exosomal lncRNA TUC339[J].Int J Mol Sci,2018,19(10):2958.
29 Liu J,Fan L,Yu H,et al.Endoplasmic reticulum stress causes liver cancer cells to release exosomal miR-23a-3p and Up-regulate programmed death ligand 1 expression in macrophages[J].Hepatology,2019,70(1):241-258.
30 Khemlina G,Ikeda S,Kurzrock R.The biology of Hepatocellular carcinoma:implications for genomic and immune therapies[J].Mol Cancer,2017,16(1):149.
31 Jiang H,Ning G,Wang Y,et al.Identification of an m6A-Related signature as biomarker for hepatocellular carcinoma prognosis and correlates with sorafenib and anti-PD-1 immunotherapy treatment response[J].Dis Markers,2021,2021:5576683.
32 Chui NN,Cheu JW,Yuen VW,et al.Inhibition of CMTM4 sensitizes cholang-iocarcinoma and hepatocellular carcinoma to T cell-mediated antitumor immunity through PD-L1[J].Hepatol Commun,2022,6(1):178-193.
33 Harding JJ,Nandakumar S,Armenia J,et al.Prospective genotyping of hepatocellular carcinoma:clinical implications of next-generation sequencing for matching patients to targeted and immune therapies[J].Clin Cancer Res,2019,25(7):2116-2126.
34 Shao YY,Liu TH,Hsu C,et al.Early alpha-foetoprotein response associated with treatment efficacy of immune checkpoint inhibitors for advanced hepato cellular carcinoma[J].Liver Int,2019,39(11):2184-2189.
35 Park SJ,Jang JY,Jeong SW,et al.Usefulness of AFP,AFP-L3,and PIVKA-II,and their combinations in diagnosing hepatocellular carcinoma[J].Medicine(Baltimore),2017,96(11):5811.
36 Feng H,Li B,Li Z,et al.PIVKA-II serves as a potential biomarker that complements AFP for the diagnosis of hepatocellular carcinoma[J].BMC Cancer,2021,21(1):401.
37 Sun X,Mei J,Lin W,et al.Reductions in AFP and PIVKA-II can predict the efficiency of anti-PD-1 immunotherapy in HCC patients[J].BMC Cancer,2021,21(1):775.
38 Chen J,Gingold JA,Su X.Immunomodulatory TGF-β signaling in hepatocellular carcinoma[J].Trends Mol Med,2019,25(11):1010-1023.
39 Bao S,Jiang X,Jin S,et al.TGF-β1 Induces immune escape by enhancing PD-1 and CTLA-4 expression on T lymphocytes in hepatocellular carcinoma[J].Front Oncol,2021,11:694145.
40 Dharmapuri S,Özbek U,Lin JY,et al.Predictive value of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in advanced hepatocellular carcinoma patients treated with anti-PD-1 therapy[J].Cancer Med,2020,9(14):4962-4970.
41 Mei J,Sun XQ,Lin WP,et al.Comparison of the prognostic value of inflammation-based scores in patients with hepatocellular carcinoma after anti-PD-1 therapy[J].J Inflamm Res,2021,14:3879-3890.
42 Schobert IT,Savic LJ,Chapiro J,et al.Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictors of tumor response in hepatocellular carcinoma after DEB-TACE[J].Eur Radiol,2020,30(10):5663-5673.
43 Zheng Y,Wang T,Tu X,et al.Gut microbiome affects the response to anti-PD-1 immunotherapy in patients with hepatocellular carcinoma[J].Immunother Cancer,2019,7(1):193.
44 Li L,Ye J.Characterization of gut microbiota in patients with primary hepatocellular carcinoma received immune checkpoint inhibitors:a Chinese population based study[J].Medicine(Baltimore),2020,99(37):21788.
45 Xu L,Leng C,Chen L,et al.Hypothyroidism is a predictive factor of superior antitumour efficacy of programmed death 1 inhibitors in hepatocellular carcinma[J].Int J Cancer,2022,150(3):472-481.
46 Lin YH,Lin KH,Yeh CT.Thyroid hormone in hepatocellular carcinoma:cancer risk,growth regulation,and anticancer drug resistance[J].Front Med(Lausanne),2020,7:174.
47 Akce M,Liu Y,Zakka K,et al.Impact of sarcopenia,BMI,and inflammatory biomarkers on survival in advanced hepatocellular carcinoma treated with anti-PD-1 antibody[J].Am J Clin Oncol,2021,44(2):74-81.
48 Cortellini A,Bersanelli M,Buti S,et al.A multicenter study of body mass index in cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors:when overweight becomes favorable[J].Immunother Cancer,2019,7(1):57.
49 Nakanishi Y,Masuda T,Yamaguchi K,et al.Albumin-globulin ratio is a predictive biomarker of antitumor effect of anti-PD-1 antibody in patients with non-small cell lung cancer[J].Int J Clin Oncol,2020,25(1):74-81.
50 Aoki T,Nishida N,Ueshima K,et al.Higher enhancement intrahepatic nodules on the hepatobiliary phase of Gd-EOB-DTPA-Enhanced MRI as a poor responsive marker of Anti-PD-1/PD-L1 monotherapy for unresectable hepa-tocellular carcinoma[J].Liver Cancer,2021,10(6):615-628.
51 Ueno A,Masugi Y,Yamazaki K,et al.OATP1B3 expression is strongly associated with Wnt/β-catenin signalling and represents the transporter of gadoxetic acid in hepatocellular carcinoma[J].Hepatol,2014,61(5):1080-1087.
52 Zou Y,Ruan S,Jin L,et al.CDK1,CCNB1,and CCNB2 are prognostic biomarkers and correlated with immune infiltration in hepatocellular carcinoma[J].Med Sci Monit,2020,26:925289.
53 Wang Y,Cao K.KDM1A promotes immunosuppression in hepatocellular carcinoma by regulating PD-L1 through Demethylating MEF2D[J].Immunol Res,2021,2021:9965099.

[1]	LIU Jiaming, CUI Yifeng, LU Zhaoyang. Aqueous Huaier extract inhibits the proliferation and metastasis of hepatocellular carcinoma by regulating the Akt signaling pathway through mitochondrial transcription factor A [J]. Journal of Practical Oncology, 2022, 36(3): 203-207.
[2]	PANG Chunhua, LI Fanrong, TANG Rubing, QIN Lei, ZHAO Xinhua, TANG Juan, YOU Xuemei. Association between preoperative fatigue status and postoperative quality of life in patients with advanced hepatocellular carcinoma:a prospective cohort study [J]. Journal of Practical Oncology, 2022, 36(2): 127-132.
[3]	LIU Yu, YU Xingxin, GENG Zhida, CHEN Zhengliang, HUI Peng, LIANG Yingjian. The role of liver fibroblasts in the occurrence and development of hepatocellular carcinoma [J]. Journal of Practical Oncology, 2022, 36(2): 167-172.
[4]	WANG Zongwen, LI Xiaodong, ZHU Qiankun, ZENG Shicong, ZHAI Bo. KIF14 in the mechanism of acquired drug resistance in hepatocellular carcinoma SMCC-7721 cells [J]. Journal of Practical Oncology, 2022, 36(1): 14-19.
[5]	LIU Fei, SUI Hong. Research progress in molecular classification of liver cancer based on tumor immunological microenvironment [J]. Journal of Practical Oncology, 2021, 35(6): 557-561.
[6]	JI Lei, JI Daolin, BAO Dongdong, TAN Gang. The latest research progress of long non-coding RNA in sorafenib resistance of hepatocellular carcinoma [J]. Journal of Practical Oncology, 2021, 35(6): 562-567.
[7]	ZHAO Haoran, LI Man, ZHANG Yubao. Research progress of hepatocellular carcinoma-related RNA binding protein [J]. Journal of Practical Oncology, 2021, 35(6): 576-579.
[8]	LU Junrong, WANG Huiwen, HE Dongfeng. Significance of high expression of SALL4 in clinicopathological and prognostic judgment of esophageal squamous cell carcinoma [J]. Journal of Practical Oncology, 2021, 35(5): 420-425.
[9]	HE Ling, YAO Kecheng. Glycosylphosphatidylinositol transamidase and hepatocellular carcinoma [J]. Journal of Practical Oncology, 2021, 35(5): 458-461.
[10]	WANG Ye, SHANG Naijian. Application progress of radiomics in the diagnosis and treatment of non-small cell lung cancer [J]. Journal of Practical Oncology, 2021, 35(5): 485-488.
[11]	WANG Mengmeng, LIAN Jie, LI Hengzhen, ZHANG Yanqiao. Research progress in immunotherapy of gastrointestinal pancreatic neuroendocrine tumors [J]. Journal of Practical Oncology, 2021, 35(2): 154-159.
[12]	ZHOU Jian,CHEN Xuejian,WANG Wei,LI Ning,SUN Zhenyu,XU Lishan. The effect of silencing PRMT5 gene in biological behavior of human hepatocellular carcinoma cells [J]. Journal of Practical Oncology, 2020, 34(3): 208-213.
[13]	ZHANG Congyi, CUI Yifeng, LI Baobao, LIU Lianxin. Expression of cell division cycle 7 protein in hepatocellular carcinoma tissues and its effect on proliferation and invasion of hepatocellular carcinoma cells [J]. Journal of Practical Oncology, 2020, 34(2): 150-155.
[14]	CHEN Ziyin, BAI Yanchun, CAO Yangsen, LI Jian, XU Lili, ZHAO Qiushuang, WANG Yang. Dosimetry advantage of respiratory gating in the treatment of hepatocellular carcinoma with large segmentation [J]. Journal of Practical Oncology, 2019, 33(6): 536-539.
[15]	QU Yanfei, LIU Chao, WANG Bojun, FANG Lin, ZHANG Yanqiao. Expression of CSN6 gene in hepatocellular carcinoma tissues and its clinical significance [J]. Journal of Practical Oncology, 2019, 33(4): 328-333.

Research status of biomarkers related to the efficacy of PD-1 inhibitors in the treatment of hepatocellular carcinoma

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments