肝细胞癌靶向/免疫治疗效果的预测指标

任鹏伟; 韩英; 周新民

doi:10.3969/j.issn.1001-5256.2023.11.028

肝细胞癌靶向/免疫治疗效果的预测指标

DOI: 10.3969/j.issn.1001-5256.2023.11.028

空军军医大学西京医院消化内科，西安 710032

基金项目:

国家自然科学基金 (81870421)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：任鹏伟负责撰写论文；韩英负责修改论文；周新民负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
周新民， zhouxmm@fmmu.edu.cn （ORCID： 0000-0002-6521-9885）

计量
- 文章访问数: 240
- HTML全文浏览量: 53
- PDF下载量: 38
- 被引次数: 0
出版历程
- 收稿日期: 2023-01-16
- 录用日期: 2023-06-09
- 出版日期: 2023-11-28

Predictive indicators for the efficacy of targeted therapy/immunotherapy for hepatocellular carcinoma

Department of Gastroenterology，Xijing Hospital，Air Force Medical University，Xi’an 710032，China

Research funding:

National Natural Science Foundation of China (81870421)

More Information

Corresponding author: ZHOU Xinmin， zhouxmm@fmmu.edu.cn （ORCID： 0000-0002-6521-9885）

摘要

摘要: 肝细胞癌（HCC）是我国常见恶性肿瘤，用于晚期HCC治疗的分子靶向药物和免疫检查点抑制剂是当下的研究热点，但治疗效果存在较大的个体差异。为进一步筛选获益人群，预测治疗效果，改善疾病预后，本文对HCC靶向/免疫治疗的效果预测相关研究进行总结，为晚期HCC患者制订个体化的治疗方案提供参考。
- 癌，肝细胞 /
- 药物疗法 /
- 免疫疗法
Abstract: Hepatocellular carcinoma （HCC） is a common malignancy in China， and molecular-targeted drugs and immune checkpoint inhibitors for the treatment of advanced HCC are currently a research hotspot； however， there are large individual differences in the treatment outcome of advanced HCC. In order to further screen for the population with benefits from such treatment， predict treatment outcome， and improve disease prognosis， this article summarizes the studies on predicting the efficacy of targeted therapy/immunotherapy for HCC， so as to provide a reference for developing individualized treatment regimens for patients with advanced HCC.
- Carcinoma， Hepatocellular /
- Drug Therapy /
- Immunotherapy

HTML全文

参考文献(36)

[1]	ZHOU M, WANG H, ZENG X, et al. Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017[J]. Lancet, 2019, 394( 10204): 1145- 1158. DOI: 10.1016/S0140-6736(19)30427-1.
[2]	RUMGAY H, ARNOLD M, FERLAY J, et al. Global burden of primary liver cancer in 2020 and predictions to 2040[J]. J Hepatol, 2022, 77( 6): 1598- 1606. DOI: 10.1016/j.jhep.2022.08.021.
[3]	General Office of National Health Commission. Standard for diagnosis and treatment of primary liver cancer(2022 edition)[J]. J Clin Hepatol, 2022, 38( 2): 288- 303. DOI: 10.3969/j.issn.1001-5256.2022.02.009. 国家卫生健康委办公厅. 原发性肝癌诊疗指南(2022年版)[J]. 临床肝胆病杂志, 2022, 38( 2): 288- 303. DOI: 10.3969/j.issn.1001-5256.2022.02.009.
[4]	LI SS, GUO ZT, CHEN ZB, et al. Research advances in systemic therapy for advanced hepatocellular carcinoma[J]. J Clin Hepatol, 2021, 37( 12): 2943- 2946. DOI: 10.3969/j.issn.1001-5256.2021.12.044. 李世思, 郭志唐, 陈章彬, 等. 晚期肝细胞癌系统治疗的研究进展[J]. 临床肝胆病杂志, 2021, 37( 12): 2943- 2946. DOI: 10.3969/j.issn.1001-5256.2021.12.044.
[5]	KUZUYA T, ISHIGAMI M, ITO T, et al. Clinical characteristics and outcomes of candidates for second-line therapy, including regorafenib and ramucirumab, for advanced hepatocellular carcinoma after sorafenib treatment[J]. Hepatol Res, 2019, 49( 9): 1054- 1065. DOI: 10.1111/hepr.13358.
[6]	HERSBERGER L, BARGETZI L, BARGETZI A, et al. Nutritional risk screening(NRS 2002) is a strong and modifiable predictor risk score for short-term and long-term clinical outcomes: secondary analysis of a prospective randomised trial[J]. Clin Nutr, 2020, 39( 9): 2720- 2729. DOI: 10.1016/j.clnu.2019.11.041.
[7]	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. DOI: 10.3322/caac.21492.
[8]	KIM B, KIM SS, CHO SW, et al. Liver stiffness in magnetic resonance elastography is prognostic for sorafenib-treated advanced hepatocellular carcinoma[J]. Eur Radiol, 2021, 31( 4): 2507- 2517. DOI: 10.1007/s00330-020-07357-9.
[9]	NICOLAS-BOLUDA A, VAQUERO J, VIMEUX L, et al. Tumor stiffening reversion through collagen crosslinking inhibition improves T cell migration and anti-PD-1 treatment[J]. Elife, 2021, 10: e58688. DOI: 10.7554/eLife.58688.
[10]	YUAN G, XIE F, SONG Y, et al. Hepatic tumor stiffness measured by shear wave elastography is prognostic for HCC progression following treatment with anti-PD-1 antibodies plus lenvatinib: A retrospective analysis of two independent cohorts[J]. Front Immunol, 2022, 13: 868809. DOI: 10.3389/fimmu.2022.868809.
[11]	WANG F, QIN S, SUN X, et al. Reactive cutaneous capillary endothelial proliferation in advanced hepatocellular carcinoma patients treated with camrelizumab: data derived from a multicenter phase 2 trial[J]. J Hematol Oncol, 2020, 13( 1): 47. DOI: 10.1186/s13045-020-00886-2.
[12]	DÍAZ-GONZÁLEZ Á, SANDUZZI-ZAMPARELLI M, SAPENA V, et al. Systematic review with meta-analysis: the critical role of dermatological events in patients with hepatocellular carcinoma treated with sorafenib[J]. Aliment Pharmacol Ther, 2019, 49( 5): 482- 491. DOI: 10.1111/apt.15088.
[13]	MAO J, WANG D, LONG J, et al. Gut microbiome is associated with the clinical response to anti-PD-1 based immunotherapy in hepatobiliary cancers[J]. J Immunother Cancer, 2021, 9( 12): e003334. DOI: 10.1136/jitc-2021-003334.
[14]	DAVID LA, MAURICE CF, CARMODY RN, et al. Diet rapidly and reproducibly alters the human gut microbiome[J]. Nature, 2014, 505( 7484): 559- 563. DOI: 10.1038/nature12820.
[15]	GALLE PR, FOERSTER F, KUDO M, et al. Biology and significance of alpha-fetoprotein in hepatocellular carcinoma[J]. Liver Int, 2019, 39( 12): 2214- 2229. DOI: 10.1111/liv.14223.
[16]	SHAO YY, LIU TH, HSU C, et al. Early alpha-foetoprotein response associated with treatment efficacy of immune checkpoint inhibitors for advanced hepatocellular carcinoma[J]. Liver Int, 2019, 39( 11): 2184- 2189. DOI: 10.1111/liv.14210.
[17]	ZHU AX, KANG YK, YEN CJ, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations(REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial[J]. Lancet Oncol, 2019, 20( 2): 282- 296. DOI: 10.1016/S1470-2045(18)30937-9.
[18]	AO H, XIN Z, JIAN Z. Liquid biopsy to identify biomarkers for immunotherapy in hepatocellular carcinoma[J]. Biomark Res, 2021, 9( 1): 91. DOI: 10.1186/s40364-021-00348-y.
[19]	YUE C, JIANG Y, LI P, et al. Dynamic change of PD-L1 expression on circulating tumor cells in advanced solid tumor patients undergoing PD-1 blockade therapy[J]. Oncoimmunology, 2018, 7( 7): e1438111. DOI: 10.1080/2162402X.2018.1438111.
[20]	WINOGRAD P, HOU S, COURT CM, et al. Hepatocellular carcinoma-circulating tumor cells expressing PD-L1 are prognostic and potentially associated with response to checkpoint inhibitors[J]. Hepatol Commun, 2020, 4( 10): 1527- 1540. DOI: 10.1002/hep4.1577.
[21]	SCHEINER B, POMEJ K, KIRSTEIN MM, et al. Prognosis of patients with hepatocellular carcinoma treated with immunotherapy-development and validation of the CRAFITY score[J]. J Hepatol, 2022, 76( 2): 353- 363. DOI: 10.1016/j.jhep.2021.09.035.
[22]	YOSHIDA T, ICHIKAWA J, GIUROIU I, et al. C reactive protein impairs adaptive immunity in immune cells of patients with melanoma[J]. J Immunother Cancer, 2020, 8( 1): e000234. DOI: 10.1136/jitc-2019-000234.
[23]	JIMENEZ RV, KUZNETSOVA V, CONNELLY AN, et al. C-reactive protein promotes the expansion of myeloid derived cells with suppressor functions[J]. Front Immunol, 2019, 10: 2183. DOI: 10.3389/fimmu.2019.02183.
[24]	AKAMINE T, TAKADA K, TOYOKAWA G, et al. Association of preoperative serum CRP with PD-L1 expression in 508 patients with non-small cell lung cancer: A comprehensive analysis of systemic inflammatory markers[J]. Surg Oncol, 2018, 27( 1): 88- 94. DOI: 10.1016/j.suronc.2018.01.002.
[25]	BRUIX J, CHENG AL, MEINHARDT G, et al. Prognostic factors and predictors of sorafenib benefit in patients with hepatocellular carcinoma: Analysis of two phase III studies[J]. J Hepatol, 2017, 67( 5): 999- 1008. DOI: 10.1016/j.jhep.2017.06.026.
[26]	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. DOI: 10.2147/JIR.S325600.
[27]	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. DOI: 10.1002/cam4.3135.
[28]	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. DOI: 10.1158/1078-0432.CCR-18-2293.
[29]	MASUDA M, CHEN WY, MIYANAGA A, et al. Alternative mammalian target of rapamycin(mTOR) signal activation in sorafenib-resistant hepatocellular carcinoma cells revealed by array-based pathway profiling[J]. Mol Cell Proteomics, 2014, 13( 6): 1429- 1438. DOI: 10.1074/mcp.M113.033845.
[30]	LLOVET JM, MONTAL R, SIA D, et al. Molecular therapies and precision medicine for hepatocellular carcinoma[J]. Nat Rev Clin Oncol, 2018, 15( 10): 599- 616. DOI: 10.1038/s41571-018-0073-4.
[31]	SCHULZE K, IMBEAUD S, LETOUZÉ E, et al. Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets[J]. Nat Genet, 2015, 47( 5): 505- 511. DOI: 10.1038/ng.3252.
[32]	PINYOL R, SIA D, LLOVET JM. Immune exclusion-Wnt/CTNNB1 class predicts resistance to immunotherapies in HCC[J]. Clin Cancer Res, 2019, 25( 7): 2021- 2023. DOI: 10.1158/1078-0432.CCR-18-3778.
[33]	SIA D, JIAO Y, MARTINEZ-QUETGLAS I, et al. Identification of an immune-specific class of hepatocellular carcinoma, based on molecular features[J]. Gastroenterology, 2017, 153( 3): 812- 826. DOI: 10.1053/j.gastro.2017.06.007.
[34]	LIU CQ, XU J, ZHOU ZG, et al. Expression patterns of programmed death ligand 1 correlate with different microenvironments and patient prognosis in hepatocellular carcinoma[J]. Br J Cancer, 2018, 119( 1): 80- 88. DOI: 10.1038/s41416-018-0144-4.
[35]	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. DOI: 10.1016/S0140-6736(17)31046-2.
[36]	YAU T, PARK JW, FINN RS, et al. Nivolumab versus sorafenib in advanced hepatocellular carcinoma(CheckMate 459): a randomised, multicentre, open-label, phase 3 trial[J]. Lancet Oncol, 2022, 23( 1): 77- 90. DOI: 10.1016/S1470-2045(21)00604-5.