Journal of Liver Cancer

Review Article

New systemic treatment options for advanced cholangiocarcinoma: Valentina Zanuso, Giulia Tesini, Elena Valenzi, Lorenza Rimassa; J Liver Cancer. 2024;24(2):155-170. Published online August 8, 2024; DOI: https://doi.org/10.17998/jlc.2024.08.07

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Cholangiocarcinoma (CCA) is a rare and aggressive cancer, mostly diagnosed at advanced or metastatic stage, at which point systemic treatment represents the only therapeutic option. Chemotherapy has been the backbone of advanced CCA treatment. More recently, immunotherapy has changed the therapeutic landscape, as immune checkpoint inhibitors have yielded the first improvement in survival and currently, the addition of either durvalumab or pembrolizumab to standard of care cisplatin plus gemcitabine represents the new first-line treatment option. However, the use of immunotherapy in subsequent lines has not demonstrated its efficacy and therefore, it is not approved, except for pembrolizumab in the selected microsatellite instability-high population. In addition, advances in comprehensive genomic profiling have led to the identification of targetable genetic alterations, such as isocitrate dehydrogenase 1 (IDH1), fibroblast growth factor receptor 2 (FGFR2), human epidermal growth factor receptor 2 (HER2), proto-oncogene B-Raf (BRAF), neurotrophic tropomyosin receptor kinase (NTRK), rearranged during transfection (RET), Kirsten rat sarcoma virus (KRAS), and mouse double minute 2 homolog (MDM2), thus favoring the development of a precision medicine approach in previously treated patients. Despite these advances, the use of molecularly driven agents is limited to a subgroup of patients. This review aims to provide an overview of the newly approved systemic therapies, the ongoing studies, and future research challenges in advanced CCA management.

Citations

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Genomic and transcriptomic signatures of sequential carcinogenesis from papillary neoplasm to biliary tract cancer
Taek Chung, Seungho Oh, Jeongsoo Won, Jiho Park, Jeong Eun Yoo, Ho Kyoung Hwang, Gi Hong Choi, Chang Moo Kang, Dai Hoon Han, Sangwoo Kim, Young Nyun Park
Journal of Hepatology.2025;[Epub] CrossRef
Is 26S proteasome non-ATPase regulatory subunit 6 a potential molecular target for intrahepatic cholangiocarcinoma?
Yong-Zhi Zhuang, Li-Quan Tong, Xue-Ying Sun
World Journal of Hepatology.2024; 16(11): 1219. CrossRef
Imaging findings of intrahepatic cholangiocarcinoma for prognosis prediction and treatment decision-making: a narrative review
Jun Gu Kang, Taek Chung, Dong Kyu Kim, Hyungjin Rhee
The Ewha Medical Journal.2024;[Epub] CrossRef
Resectability and survival outcome in real world practice of 720 cholangiocarcinoma patients: intrahepatic, perihilar and distal cholangiocarcinoma.
Poowanai Sarkhampee, Weeris Ouransatien, Nithi Lertsawatvicha, Satsawat Chansitthichock, Paiwan Wattanarath
World Journal of Surgical Oncology.2024;[Epub] CrossRef

Original Articles

Cure can be achieved by conversion to microwave ablation following atezolizumab-bevacizumab therapy in unresectable hepatocellular carcinoma: Rene John D. Febro, Engelbert Simon S. Perillo, Akemi A. Kimura, Stephen N. Wong; J Liver Cancer. 2024;24(2):234-242. Published online June 3, 2024; DOI: https://doi.org/10.17998/jlc.2024.05.23

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129 Downloads

Abstract PDF: Backgrounds/Aims
Atezolizumab/bevacizumab is the recommended first-line systemic therapy for unresectable hepatocellular carcinoma (uHCC) and may facilitate curative conversion through resection and locoregional therapies. However, there have been very few reports on curative conversion using microwave ablation (MWA). This study aimed to determine the curative conversion rate with MWA using atezolizumab-bevacizumab as the first-line treatment in patients with uHCC, and to compare the characteristics and survival of patients with and without curative conversion.
Methods
Consecutive patients with uHCC who were started on atezolizumab-bevacizumab from May 2021 to December 2023 in a single tertiary center were included. Objective response rate (ORR) and disease control rate (DCR) were based on the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) criteria.
Results
Twenty consecutive patients with uHCC (60% advanced-stage) were included, 90% exceeding the up-to-7 criteria. The ORR and DCR were 35% and 60%, 35% and 55% using RECIST and mRECIST, respectively. Five patients (25%) underwent successful curative conversion with MWA (four advanced and one intermediate stage) despite a median HCC size of 6.1 cm (range, 2.4-7.3). Two of these patients were tumor and drug-free 132-133 weeks from the 1st atezolizumab-bevacizumab dose. Patients who underwent curative conversion had significantly longer survival than those who did not (P=0.024). Other factors associated with survival were male sex, Child-Pugh class A, and an objective response.
Conclusions
Despite the relatively large tumor size, successful curative conversion with MWA was achieved with first-line atezolizumab-bevacizumab in uHCC. However, data from prospective multicenter trials are required to determine whether this strategy is universally applicable.

Comparison of atezolizumab plus bevacizumab and lenvatinib for hepatocellular carcinoma with portal vein tumor thrombosis: Jeayeon Park, Yun Bin Lee, Yunmi Ko, Youngsu Park, Hyunjae Shin, Moon Haeng Hur, Min Kyung Park, Dae-Won Lee, Eun Ju Cho, Kyung-Hun Lee, Jeong-Hoon Lee, Su Jong Yu, Tae-Yong Kim, Yoon Jun Kim, Tae-You Kim, Jung-Hwan Yoon; J Liver Cancer. 2024;24(1):81-91. Published online January 19, 2024; DOI: https://doi.org/10.17998/jlc.2023.12.25

3,604 Views
226 Downloads
3 Citations

Abstract PDF Supplementary Material

Background/Aim
Atezolizumab plus bevacizumab and lenvatinib are currently available as first-line therapy for the treatment of unresectable hepatocellular carcinoma (HCC). However, comparative efficacy studies are still limited. This study aimed to investigate the effectiveness of these treatments in HCC patients with portal vein tumor thrombosis (PVTT).
Methods
We retrospectively included patients who received either atezolizumab plus bevacizumab or lenvatinib as first-line systemic therapy for HCC with PVTT. Primary endpoint was overall survival (OS), and secondary endpoints included progressionfree survival (PFS) and disease control rate (DCR) determined by response evaluation criteria in solid tumors, version 1.1.
Results
A total of 52 patients were included: 30 received atezolizumab plus bevacizumab and 22 received lenvatinib. The median follow-up duration was 6.4 months (interquartile range, 3.9-9.8). The median OS was 10.8 months (95% confidence interval [CI], 5.7 to not estimated) with atezolizumab plus bevacizumab and 5.8 months (95% CI, 4.8 to not estimated) with lenvatinib (P=0.26 by log-rank test). There was no statistically significant difference in OS (adjusted hazard ratio [aHR], 0.71; 95% CI, 0.34-1.49; P=0.37). The median PFS was similar (P=0.63 by log-rank test), with 4.1 months (95% CI, 3.3-7.7) for atezolizumab plus bevacizumab and 4.3 months (95% CI, 2.6-5.8) for lenvatinib (aHR, 0.93; 95% CI, 0.51-1.69; P=0.80). HRs were similar after inverse probability treatment weighting. The DCRs were 23.3% and 18.2% in patients receiving atezolizumab plus bevacizumab and lenvatinib, respectively (P=0.74).
Conclusion
The effectiveness of atezolizumab plus bevacizumab and lenvatinib was comparable for the treatment of HCC with PVTT.

Citations

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Portal vein tumor thrombosis in hepatocellular carcinoma patients: Is it the end?
Walaa Abdelhamed, Hend Shousha, Mohamed El-Kassas
Liver Research.2024;[Epub] CrossRef
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Jin Hyoung Kim, Gun Ha Kim, Dong Il Gwon
Clinical and Molecular Hepatology.2024; 30(4): 659. CrossRef
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Review Articles

Complications of immunotherapy in advanced hepatocellular carcinoma: Young-Gi Song, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim; J Liver Cancer. 2024;24(1):9-16. Published online November 29, 2023; DOI: https://doi.org/10.17998/jlc.2023.11.21

3,290 Views
186 Downloads
9 Citations

Abstract PDF

Immune checkpoint inhibitors (ICIs) are highly effective in cancer treatment. However, the risks associated with the treatment must be carefully balanced against the therapeutic benefits. Immune-related adverse events (irAEs) are generally unpredictable and may persist over an extended period. In this review, we analyzed common irAEs reported in highly cited original articles and systematic reviews. The prevalent adverse reactions include fatigue, pyrexia, rash, pruritus, diarrhea, decreased appetite, nausea, abdominal pain, constipation, hepatitis, and hypothyroidism. Therefore, it is crucial to conduct evaluations not only of gastrointestinal organs but also of cardiac, neurologic, endocrine (including the frequently affected thyroid), and ophthalmic systems before commencing ICIs. This review further explores commonly reported types of irAEs, specific irAEs associated with each ICI agent, rare yet potentially fatal irAEs, and available treatment options for managing them.

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METTL3-mediated SMPDL3A promotes cell growth, metastasis and immune process of hepatocellular carcinoma by regulating LRPPRC
Weixin Xu, Miaomiao Tao, Yeqiong Liu, Jun Yan, Jiali Hu, Lei Wang
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Intrahepatic IgA complex induces polarization of cancer-associated fibroblasts to matrix phenotypes in the tumor microenvironment of HCC
Jong Geun Park, Pu Reun Roh, Min Woo Kang, Sung Woo Cho, Suhyun Hwangbo, Hae Deok Jung, Hyun Uk Kim, Ji Hoon Kim, Jae-Sung Yoo, Ji Won Han, Jeong Won Jang, Jong Young Choi, Seung Kew Yoon, Young Kyoung You, Ho Joong Choi, Jae Yong Ryu, Pil Soo Sung
Hepatology.2024; 80(5): 1074. CrossRef
Risk of Bleeding in Hepatocellular Carcinoma Patients Treated with Atezolizumab/Bevacizumab: A Systematic Review and Meta-Analysis
Young-Gi Song, Kyeong-Min Yeom, Eun Ae Jung, Sang Gyune Kim, Young Seok Kim, Jeong-Ju Yoo
Liver Cancer.2024; : 1. CrossRef
Targeted therapies in hepatocellular carcinoma: past, present, and future
Rushabh Gujarathi, Joseph W. Franses, Anjana Pillai, Chih-Yi Liao
Frontiers in Oncology.2024;[Epub] CrossRef
Atezolizumab-Induced Ulcerative Colitis in Patient with Hepatocellular Carcinoma: Case Report and Literature Review
Hyuk Kim, Yoon E Shin, Hye-Jin Yoo, Jae-Young Kim, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
Medicina.2024; 60(9): 1422. CrossRef
A Potential Pneumothorax Induced by Immune Checkpoint Inhibitors: A Case Report and Literature Review
Yoon-E Shin, Hyuk Kim, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
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The histopathological and molecular heterogeneity of hepatocellular carcinoma: a narrative review
Wonju Chung, Haeryoung Kim
The Ewha Medical Journal.2024;[Epub] CrossRef
Pathogenesis and management of metabolic dysfunction-associated steatohepatitis-related hepatocellular carcinoma: a narrative review
Han Ah Lee
The Ewha Medical Journal.2024;[Epub] CrossRef
Current perspectives on the pharmacological treatment of advanced hepatocellular carcinoma: a narrative review
Hye-Jin Yoo, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
The Ewha Medical Journal.2024;[Epub] CrossRef

A multidisciplinary approach with immunotherapies for advanced hepatocellular carcinoma: Yu Rim Lee; J Liver Cancer. 2023;23(2):316-329. Published online September 22, 2023; DOI: https://doi.org/10.17998/jlc.2023.09.04

2,936 Views
146 Downloads
10 Citations

Abstract PDF

Hepatocellular carcinoma (HCC) is a highly aggressive disease that is usually diagnosed at an advanced stage. Advanced HCC has limited treatment options and often has a poor prognosis. For the past decade, tyrosine kinase inhibitors have been the only treatments approved for advanced HCC that have shown overall survival (OS) benefits; however, but their clinical efficacy has been limited. Recent trials have demonstrated promising advancements in survival outcomes through immunotherapy-based treatments, such as combinations of immune checkpoint inhibitors (ICIs) with other ICIs, antiangiogenic drugs, and locoregional therapies. The atezolizumab-bevacizumab and durvalumab-tremelimumab (STRIDE) regimen has significantly improved survival rates as a first-line treatment and has become the new standard of care. Therefore, combined treatments for advanced HCC can result in better treatment outcomes owing to their synergistic effects, which requires a multidisciplinary approach. Ongoing studies are examining other therapeutic innovations that can improve disease control and OS rates. Despite improvements in the treatment of advanced HCC, further studies on the optimal treatment selection and sequences, biomarker identification, combination approaches with other therapies, and development of novel immunotherapy agents are required. This review presents the current treatment options and clinical data of the ICI-based combination immunotherapies for advanced HCC from a multidisciplinary perspective.

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Journal of Cellular and Molecular Medicine.2024;[Epub] CrossRef
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Hyuk Kim, Yoon E Shin, Hye-Jin Yoo, Jae-Young Kim, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
Medicina.2024; 60(9): 1422. CrossRef
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Prediction of PD-L1 expression in unresectable hepatocellular carcinoma with gadoxetic acid-enhanced MRI
Jun Gu Kang, Kyunghwa Han, Taek Chung, Hyungjin Rhee
European Journal of Radiology.2024; 181: 111772. CrossRef
Advances in Understanding Hepatocellular Carcinoma Vasculature: Implications for Diagnosis, Prognostication, and Treatment
Hyungjin Rhee, Young Nyun Park, Jin-Young Choi
Korean Journal of Radiology.2024; 25(10): 887. CrossRef
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Hye-Jin Yoo, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
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Improved survival with second-line hepatic arterial infusion chemotherapy after atezolizumab-bevacizumab failure in hepatocellular carcinoma
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Frontiers in Oncology.2024;[Epub] CrossRef

The role of lenvatinib in the era of immunotherapy of hepatocellular carcinoma: Matthew Man Pok Lee, Landon Long Chan, Stephen Lam Chan; J Liver Cancer. 2023;23(2):262-271. Published online August 17, 2023; DOI: https://doi.org/10.17998/jlc.2023.07.17

5,100 Views
338 Downloads
13 Citations

Abstract PDF

Hepatocellular carcinoma (HCC) frequently presents as advanced stage with poor prognosis and high mortality. Systemic treatment is the treatment of choice for advanced disease. In 2007, the first multi-kinase inhibitor (MKI) sorafenib was approved and shown to modestly prolong overall survival (OS). The progress of systemic therapy has been slow afterwards until 2018 when lenvatinib, another MKI, was shown to be non-inferior to sorafenib on median OS as the first-line therapy for HCC. Since then, remarkable progress has been achieved on the treatment of advanced HCC, including the development of second-line targeted treatment, including regorafenib, cabozantinib and ramucirumab from 2017 to 2019. A growing focus has been placed on immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1), its ligand PD-L1, and cytotoxic T-lymphocyte-associated protein 4. These ICIs have proven their potency in treating HCC as both initial and subsequent line of therapy. At present, both regimens of atezolizumab combined with bevacizumab, as well as the combination of tremelimumab and durvalumab, are recommended as the first-line treatments based on positive phase III clinical trials. With the advancement of ICIs, it is anticipated that the role of MKIs in the treatment of HCC will evolve. In this article, lenvatinib, one of the most commonly used MKIs in HCC, is chosen to be reviewed.

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Bidirectional regulation of the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon gene pathway and its impact on hepatocellular carcinoma
Ai-Yu Nie, Zhong-Hui Xiao, Jia-Li Deng, Na Li, Li-Yuan Hao, Sheng-Hao Li, Xiao-Yu Hu
World Journal of Gastrointestinal Oncology.2025;[Epub] CrossRef
Reduced-Dose or Discontinuation of Bevacizumab Might Be Considered after Variceal Bleeding in Patients with Hepatocellular Carcinoma Receiving Atezolizumab/Bevacizumab: Case Reports
Kyeong-Min Yeom, Young-Gi Song, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
Medicina.2024; 60(1): 157. CrossRef
The Position of Multikinase Inhibitors in the Era of Immune-Checkpoint Inhibitors for Hepatocellular Carcinoma
Beom Kyung Kim
Gut and Liver.2024; 18(1): 3. CrossRef
Fatal intratumoral hemorrhage in a patient with hepatocellular carcinoma following successful treatment with atezolizumab/bevacizumab: A case report
Kyeong-Hoon Park, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
World Journal of Clinical Cases.2024; 12(22): 5177. CrossRef
Small molecule tyrosine kinase inhibitors approved for systemic therapy of advanced hepatocellular carcinoma: recent advances and future perspectives
Jianzhong Liu, Shuai Xia, Baoyi Zhang, Dina Mostafa Mohammed, Xiangliang Yang, Yanhong Zhu, Xinnong Jiang
Discover Oncology.2024;[Epub] CrossRef
Consistent efficacy of hepatic artery infusion chemotherapy irrespective of PD‑L1 positivity in unresectable hepatocellular carcinoma
Ji Kim, Young Kim, Hee-Chul Nam, Chang-Wook Kim, Jae-Sung Yoo, Ji Han, Jeong Jang, Jong Choi, Seung Yoon, Ho Jong Chun, Jung Oh, Suho Kim, Sung Lee, Pil Sung
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Jinbiao Chen, Ken Liu, Mathew A. Vadas, Jennifer R. Gamble, Geoffrey W. McCaughan
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Role of transarterial chemoembolization for hepatocellular carcinoma with extrahepatic metastases in the era of advancing systemic therapy
Byeong Geun Song, Myung Ji Goh, Wonseok Kang, Dong Hyun Sinn, Geum-Youn Gwak, Yong-Han Paik, Joon Hyeok Lee, Moon Seok Choi
Journal of Liver Cancer.2024; 24(2): 243. CrossRef
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Junjie Ao, Na Qiang, Hiroaki Kanzaki, Masato Nakamura, Risa Kakiuchi, Jiaqi Zhang, Ryuta Kojima, Keisuke Koroki, Masanori Inoue, Naoya Kanogawa, Ryo Nakagawa, Takayuki Kondo, Sadahisa Ogasawara, Shingo Nakamoto, Ryosuke Muroyama, Jun Kato, Naoya Kato
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Challenges and advances of immune checkpoint therapy
Lingyu Li, Yingli Sun
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Case Report

Concurrent transarterial radioembolization and combination atezolizumab/ bevacizumab treatment of infiltrative hepatocellular carcinoma with portal vein tumor thrombosis: a case report: Min Kyung Park, Su Jong Yu; J Liver Cancer. 2022;22(1):69-74. Published online March 21, 2022; DOI: https://doi.org/10.17998/jlc.2022.03.09

4,576 Views
121 Downloads
4 Citations

Abstract PDF

Treatment options for advanced hepatocellular carcinoma (HCC) have been rapidly evolving. Herein, we describe a patient with advanced HCC and portal vein tumor thrombosis (PVTT) who responded decisively to a multidisciplinary approach. The patient had an ill-defined infiltrative HCC (diffuse subtype), with several intrahepatic metastasis and tumor invasion of left portal vein. Concurrent use of transarterial radioembolization (TARE) and systemic therapeutics (atezolizumab + bevacizumab) ultimately proved successful. There was marked reduction in tumor volume after TARE and an additional three cycles of atezolizumab plus bevacizumab. This concurrent treatment was well tolerated, without adverse events during immunotherapy. The impressive results achieved suggest that concurrent TARE and combination atezolizumab/bevacizumab is a promising treatment approach for advanced HCC with PVTT.

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Rajangad S. Gurtatta, Sydney E. Whalen, Charles E. Ray
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Combining Immunotherapy with Transarterial Radioembolization
Zeynep Ceren Balaban Genc, Efe Soydemır, Seval Ay Ersoy, Tunc Ones
Indian Journal of Nuclear Medicine.2023; 38(2): 145. CrossRef
The New Era of Systemic Treatment for Hepatocellular Carcinoma: From the First Line to the Optimal Sequence
Maria Cerreto, Ferdinando Cardone, Lucia Cerrito, Leonardo Stella, Francesco Santopaolo, Maria Pallozzi, Antonio Gasbarrini, Francesca Romana Ponziani
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Is multidisciplinary treatment effective for hepatocellular carcinoma with portal vein tumor thrombus?
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Review Articles

Advances in immune checkpoint inhibitors for hepatocellular carcinoma: Ji Won Han, Su-Hyung Park; J Liver Cancer. 2021;21(2):139-145. Published online September 30, 2021; DOI: https://doi.org/10.17998/jlc.2021.09.24

4,828 Views
109 Downloads
5 Citations

Abstract PDF

Hepatocellular carcinoma (HCC) is the fifth most common cancer, and the second leading cause of cancer-related death worldwide. Although recent advances in immune checkpoint inhibitor-based immunotherapy have initiated a new era for advanced HCC treatment, the majority of HCC patients receiving immune checkpoint blockades do not derive clinical benefit. Thus, there remains an urgent need for novel immunotherapeutic strategies with improved therapeutic efficacy. Here we review recent studies of immune checkpoint blockade in HCC, providing the necessary basis for the rational design of immunotherapy.

Citations

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Role of transarterial chemoembolization for hepatocellular carcinoma with extrahepatic metastases in the era of advancing systemic therapy
Byeong Geun Song, Myung Ji Goh, Wonseok Kang, Dong Hyun Sinn, Geum-Youn Gwak, Yong-Han Paik, Joon Hyeok Lee, Moon Seok Choi
Journal of Liver Cancer.2024; 24(2): 243. CrossRef
Dynamic Peripheral T-Cell Analysis Identifies On-Treatment Prognostic Biomarkers of Atezolizumab plus Bevacizumab in Hepatocellular Carcinoma
Ji Won Han, Min Woo Kang, Soon Kyu Lee, Hyun Yang, Ji Hoon Kim, Jae-Sung Yoo, Hee Sun Cho, Eun Ji Jang, Deok Hwa Seo, Jung Hyun Kwon, Soon Woo Nam, Si Hyun Bae, Jeong Won Jang, Jong Young Choi, Seung Kew Yoon, Pil Soo Sung
Liver Cancer.2024; : 1. CrossRef
Systematic Review of Molecular Targeted Therapies for Adult-Type Diffuse Glioma: An Analysis of Clinical and Laboratory Studies
Logan Muzyka, Nicolas K. Goff, Nikita Choudhary, Michael T. Koltz
International Journal of Molecular Sciences.2023; 24(13): 10456. CrossRef
Integrative analysis of lactylation-related genes and establishment of a novel prognostic signature for hepatocellular carcinoma
Diankui Cai, Xiaoqing Yuan, D. Q. Cai, Ang Li, Sijia Yang, Weibang Yang, Jinxin Duan, Wenfeng Zhuo, Jun Min, Li Peng, Jinxing Wei
Journal of Cancer Research and Clinical Oncology.2023; 149(13): 11517. CrossRef
Editorial on Immune Checkpoint Inhibitors in the Treatment of Hepatocellular Carcinoma
Samantha M Ruff, Timothy M Pawlik
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Systemic therapy for advanced hepatocellular carcinoma: consideration for selecting second-line treatment: Bo Hyun Kim, Joong-Won Park; J Liver Cancer. 2021;21(2):124-138. Published online September 30, 2021; DOI: https://doi.org/10.17998/jlc.2021.09.23

5,027 Views
125 Downloads
2 Citations

Abstract PDF

Several molecular-targeted agents have been tested as first- or second-line therapies for hepatocellular carcinoma (HCC) but failed to improve clinical outcomes; sorafenib has been the only approved systemic agent for treating HCC for almost 10 years. Regorafenib resulted in a significant improvement in overall survival and thus was approved for HCC patients previously treated with sorafenib. Subsequently, cabozantinib and ramucirumab demonstrated superior overall survival compared with placebos in phase III clinical trials. Immune checkpoint inhibitors such as nivolumab with or without ipilimumab and pembrolizumab are also available in some countries for patients who are unresponsive to sorafenib. Some second-line agents are available for patients who are unresponsive to sorafenib; however, little is known about the considerations for selecting appropriate secondline systemic agents. Hence, this study aimed to review the current and future perspectives of second-line systemic agents.

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Expression of Peptidyl Arginine Deiminase 2 Is Closely Associated with Recurrence in Patients with Hepatocellular Carcinoma
Sunho Uhm, Yoon Cho, Ji-Young Choe, Ji Park, Min-Jeong Kim, Won-Ho Han, Junyong Lee, Jung Lee, Dong Shin, Jae Soh, Hyun Lim, Ho Kang, Sung-Hoon Moon, Sung-Eun Kim
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Expert consensus on the management of adverse events in patients receiving lenvatinib for hepatocellular carcinoma
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Deciphering and Reversing Immunosuppressive Cells in the Treatment of Hepatocellular Carcinoma: Su Jong Yu, Tim F. Greten; J Liver Cancer. 2020;20(1):1-16. Published online March 31, 2020; DOI: https://doi.org/10.17998/jlc.20.1.1

8,085 Views
201 Downloads
3 Citations

Abstract PDF

Use of immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC) has been partially successful. However, most HCC patients do not respond to immunotherapy. HCC has been shown to induce several immune suppressor mechanisms in patients. These suppressor mechanisms include involvement of myeloid-derived suppressor cells, regulatory T-cells, functionally impaired dendritic cells (DCs), neutrophils, monocytes, and tumor associated macrophages. The accumulation of immunosuppressive cells may lead to an immunosuppressive tumor microenvironment as well as the dense fibrotic stroma which may contribute to immune tolerance. Our laboratory has been investigating different cellular mechanisms of immune suppression in HCC patients. In vitro as well as in vivo studies have demonstrated that abrogation of the suppressor cells enhances or unmasks tumor-specific antitumor immune responses. Two or three effective systemic therapies including ICIs and/or molecular targeted therapies and the addition of innovative combination therapies targeting immune suppressor cells may lead to increased immune recognition with a greater tumor response. We reviewed the literature for the latest research on immune suppressor cells in HCC, and here we provide a comprehensive summary of the recent studies in this field.

Citations

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Higher Number of Tumor-Infiltrating PD-L1+ Cells Is Related to Better Response to Multikinase Inhibitors in Hepatocellular Carcinoma
Ji Won Han, Ji Hoon Kim, Dong Hyun Kim, Jeong Won Jang, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon, Jaegyoon Ahn, Hyun Yang, Pil Soo Sung
Diagnostics.2023; 13(8): 1453. CrossRef
Immune checkpoint inhibitors in HCC: Cellular, molecular and systemic data
Uasim Harkus, Miriam Wankell, Pranavan Palamuthusingam, Craig McFarlane, Lionel Hebbard
Seminars in Cancer Biology.2022; 86: 799. CrossRef
Crosstalk between tumor-associated macrophages and neighboring cells in hepatocellular carcinoma
Pil Soo Sung
Clinical and Molecular Hepatology.2022; 28(3): 333. CrossRef

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