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Cui H, Li S, Lv W, Xiang J. Association of hepatitis B virus DNA levels with efficacy and safety and the impact of antiviral therapy on prognosis in liver cancer patients receiving immune checkpoint inhibitors therapy: a systematic review and meta-analysis. Front Microbiol 2025; 16:1501139. [PMID: 39911258 PMCID: PMC11794511 DOI: 10.3389/fmicb.2025.1501139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 01/08/2025] [Indexed: 02/07/2025] Open
Abstract
Background The current evidence regarding the relationship between baseline hepatitis B virus (HBV) DNA levels and survival outcomes in liver cancer patients receiving immune checkpoint inhibitors (ICIs) remains inconsistent. Therefore, this review was intended to explore the impact of the baseline HBV-DNA level on the efficacy and safety of ICIs in patients with liver cancer. Methods Relevant studies were identified through a comprehensive search in PubMed, EMBASE, Cochrane Library, and Web of Science up to August 1, 2024. The outcomes were hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), as well as odds ratios (ORs) for objective response rate (ORR), disease control rate (DCR) and HBV reactivation (HBVr). Subgroup analysis, publication bias, and sensitivity analysis were conducted with STATA 14.0. Results This meta-analysis comprised 17 articles involving a total of 2,130 patients. The pooled results demonstrated that high HBV DNA was associated with a worse OS (HR = 1.48 95% CI 1.11-1.96). Further subgroup analysis showed that there was no difference in OS between the high HBV DNA group and low HBV DNA group when all patients received antiviral treatment. No associations between baseline HBV DNA and PFS (HR = 1.08, 95% CI 0.90-1.29), ORR (OR = 0.91, 95% CI 0.65-1.28), or DCR (OR = 0.83, 95% CI 0.58-1.20) were observed. The risk of HBVr in the high HBV DNA group was lower than that in the low HBV DNA group (OR = 0.30, 95% CI 0.15-0.58), especially among patients who received antiviral therapy (OR = 0.42, 95% CI 0.18-0.98). Conclusion High HBV DNA was associated with worse OS, but not with PFS, ORR, or DCR in liver cancer patients receiving ICIs. When patients were simultaneously treated with antiviral treatment, elevated HBV DNA level had no unfavorable impact on the efficacy of ICIs. Furthermore, the risk of HBVr in the high HBV-DNA group was lower than that in the low HBV DNA group. More prospective studies with larger sample sizes are essential to confirm the results.
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Affiliation(s)
- Hongxia Cui
- Department of Pharmacy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China
| | - Su Li
- Department of Pharmacy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China
| | - Wu Lv
- Department of General Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China
| | - Jing Xiang
- Department of Pharmacy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China
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Ji Z, Li J, Zhang S, Jia Y, Zhang J, Guo Z. The load of hepatitis B virus reduces the immune checkpoint inhibitors efficiency in hepatocellular carcinoma patients. Front Immunol 2024; 15:1480520. [PMID: 39664382 PMCID: PMC11632129 DOI: 10.3389/fimmu.2024.1480520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 11/07/2024] [Indexed: 12/13/2024] Open
Abstract
Introduction Chronic viral infection may lead to an immunosuppressive microenvironment, whereas the association between virus-related indicators and treatment response in hepatocellular carcinoma(HCC) patients undergoing immune checkpoint inhibitors(ICIs) therapy remains a topic of debate. We aim to investigate the influence of hepatitis virus on the ICI efficiency in HCC patients through a meta-analysis. Methods We searched PubMed, Cochrane Library, Embase, and Web of Science until 14 July 2024 to identify cohort studies involving ICIs treatments in HCC patients. We extracted data from the literature related to hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, baseline HBV load, and antiviral therapy. Overall survival (OS) and progression-free survival (PFS) were considered as the primary endpoints, while objective response rate (ORR) was regarded as a secondary endpoint. Results We included 55 cohort studies published between 2019 and 2024, involving a patient population of 7180 individuals. Summarized hazard ratio (HR) comparing HBV infection with non-HBV infection in the context of ICIs therapy revealed no significant association between HBV infection and either mortality risk or progression risk with the pooled HR for OS of 1.04(95%CI: 0.93-1.16, P=0.483) and the pooled HR for PFS of 1.07(95%CI:0.96-1.20, P=0.342). HBV infected patients with HCC may have better tumor response than non-HBV infected patients receiving ICIs with the combined relative risk(RR) for ORR was 1.94 (95%CI: 1.12-3.38, P=0.002). High baseline HBV load is associated with poor survival outcomes in patients with HCC who receive ICIs with the pooled HR for OS was 1.74 (95%CI: 1.27-2.37, P=0.001), thereby antiviral therapy has the potential to significantly enhance prognostic outcomes with the pooled HR for OS was 0.24 (95% CI: 0.14-0.42 P<0.001) and the pooled HR for PFS was 0.54 (95% CI: 0.33-0.89 P=0.014). Conclusion In individuals with HCC who received ICIs, there was no notable link found between HBV or HCV infection and prognosis. However, HBV infection showed a connection with improved tumor response. A higher initial HBV load is linked to worse survival results in HCC patients undergoing ICIs treatment and antiviral therapy can significantly improve its prognosis.
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Affiliation(s)
- Zhengzheng Ji
- Department of Rheumatology and Immunology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Jiasong Li
- Department of Rheumatology and Immunology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Shasha Zhang
- Department of Rheumatology and Immunology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yuanyuan Jia
- Department of Rheumatology and Immunology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Jing Zhang
- Department of Gerontology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Zhanjun Guo
- Department of Rheumatology and Immunology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
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Pan D, Liu HN, Yao ZY, Chen XX, Li YQ, Zhu JJ, Han ZX, Qin XB. Impact of baseline hepatitis B virus viral load on the long-term prognosis of advanced hepatocellular carcinoma treated with immunotherapy. World J Gastrointest Oncol 2024; 16:2504-2519. [PMID: 38994160 PMCID: PMC11236260 DOI: 10.4251/wjgo.v16.i6.2504] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Revised: 04/21/2024] [Accepted: 04/26/2024] [Indexed: 06/14/2024] Open
Abstract
BACKGROUND Although the combination of lenvatinib and PD-1 inhibitors has become the standard regimen for the treatment of advanced hepatocellular carcinoma (HCC), real data on the impact of baseline hepatitis B virus (HBV)-DNA levels on the clinical efficacy of this regimen is still limited. AIM To evaluate the effectiveness of camrelizumab combined with lenvatinib in patients with HCC at varying levels of HBV-DNA. METHODS One hundred and twenty patients with HCC who received camrelizumab and lenvatinib treatment were categorized into two cohorts: HBV-DNA ≤ 2000 (n = 66) and HBV-DNA > 2000 (n = 54). The main outcomes measured were overall survival (OS) and progression-free survival (PFS), while additional outcomes included the rate of objective response rate (ORR), disease control rate (DCR), and any negative events. Cox proportional hazards regression analysis revealed independent predictors of OS, leading to the creation of a nomogram incorporating these variables. RESULTS The median PFS was 8.32 months for the HBV-DNA ≤ 2000 group, which was similar to the 7.80 months observed for the HBV DNA > 2000 group (P = 0.88). Likewise, there was no notable variation in the median OS between the two groups, with durations of 13.30 and 14.20 months respectively (P = 0.14). The ORR and DCR were compared between the two groups, showing ORR of 19.70% vs 33.33% (P = 0.09) and DCR of 72.73% vs 74.07% (P = 0.87). The nomogram emphasized the importance of antiviral treatment as the main predictor of patient results, with portal vein tumor thrombus and Barcelona Clinic Liver Cancer staging following closely behind. CONCLUSION The clinical outcomes of patients with HBV-associated HCC treated with camrelizumab in combination with lenvatinib are not significantly affected by HBV viral load.
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Affiliation(s)
- Di Pan
- Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
| | - Hao-Nan Liu
- Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
| | - Zhi-Yuan Yao
- Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
| | - Xiao-Xiao Chen
- Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
| | - Yu-Qi Li
- Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
| | - Jing-Jing Zhu
- Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
| | - Zheng-Xiang Han
- Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
| | - Xiao-Bing Qin
- Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
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Pan D, Liu HN, Yao ZY, Chen XX, Li YQ, Zhu JJ, Han ZX, Qin XB. Impact of baseline hepatitis B virus viral load on the long-term prognosis of advanced hepatocellular carcinoma treated with immunotherapy. World J Gastrointest Oncol 2024; 16:2492-2507. [DOI: 10.4251/wjgo.v16.i6.2492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Revised: 04/21/2024] [Accepted: 04/26/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND Although the combination of lenvatinib and PD-1 inhibitors has become the standard regimen for the treatment of advanced hepatocellular carcinoma (HCC), real data on the impact of baseline hepatitis B virus (HBV)-DNA levels on the clinical efficacy of this regimen is still limited.
AIM To evaluate the effectiveness of camrelizumab combined with lenvatinib in patients with HCC at varying levels of HBV-DNA.
METHODS One hundred and twenty patients with HCC who received camrelizumab and lenvatinib treatment were categorized into two cohorts: HBV-DNA ≤ 2000 (n = 66) and HBV-DNA > 2000 (n = 54). The main outcomes measured were overall survival (OS) and progression-free survival (PFS), while additional outcomes included the rate of objective response rate (ORR), disease control rate (DCR), and any negative events. Cox proportional hazards regression analysis revealed independent predictors of OS, leading to the creation of a nomogram incorporating these variables.
RESULTS The median PFS was 8.32 months for the HBV-DNA ≤ 2000 group, which was similar to the 7.80 months observed for the HBV DNA > 2000 group (P = 0.88). Likewise, there was no notable variation in the median OS between the two groups, with durations of 13.30 and 14.20 months respectively (P = 0.14). The ORR and DCR were compared between the two groups, showing ORR of 19.70% vs 33.33% (P = 0.09) and DCR of 72.73% vs 74.07% (P = 0.87). The nomogram emphasized the importance of antiviral treatment as the main predictor of patient results, with portal vein tumor thrombus and Barcelona Clinic Liver Cancer staging following closely behind.
CONCLUSION The clinical outcomes of patients with HBV-associated HCC treated with camrelizumab in combination with lenvatinib are not significantly affected by HBV viral load.
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Affiliation(s)
- Di Pan
- Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
| | - Hao-Nan Liu
- Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
| | - Zhi-Yuan Yao
- Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
| | - Xiao-Xiao Chen
- Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
| | - Yu-Qi Li
- Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
| | - Jing-Jing Zhu
- Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
| | - Zheng-Xiang Han
- Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
| | - Xiao-Bing Qin
- Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
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Han CL, Tian BW, Yan LJ, Ding ZN, Liu H, Mao XC, Tian JC, Xue JS, Tan SY, Dong ZR, Yan YC, Hong JG, Chen ZQ, Wang DX, Li T. Efficacy and safety of immune checkpoint inhibitors for hepatocellular carcinoma patients with macrovascular invasion or extrahepatic spread: a systematic review and meta-analysis of 54 studies with 6187 hepatocellular carcinoma patients. Cancer Immunol Immunother 2023; 72:1957-1969. [PMID: 36811662 PMCID: PMC10991272 DOI: 10.1007/s00262-023-03390-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 01/27/2023] [Indexed: 02/24/2023]
Abstract
BACKGROUND AND AIMS The impacts of macrovascular invasion (MVI) or extrahepatic spread (EHS) on the efficacy and safety of immune checkpoint inhibitors (ICIs) among hepatocellular carcinoma (HCC) patients remain unclear. Thus, we conducted a systematic review and meta-analysis to clarify whether ICI therapy is a feasible treatment option for HCC with MVI or EHS. METHODS Eligible studies published before September 14, 2022, were retrieved. In this meta-analysis, the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and occurrence of adverse events (AEs) were outcomes of interest. RESULTS Fifty-four studies involving 6187 individuals were included. The findings indicated that the presence of EHS in ICI-treated HCC patients may indicate an inferior ORR (OR 0.77, 95% CI 0.63-0.96), but may not significantly affect the PFS (multivariate analyses: HR 1.27, 95% CI 0.70-2.31) and OS (multivariate analyses: HR 1.23, 95% CI 0.70-2.16). Additionally, the presence of MVI in ICI-treated HCC patients may not have significant prognostic impact on ORR (OR 0.84, 95% CI 0.64-1.10), but may indicate inferior PFS (multivariate analyses: HR 1.75, 95% CI 1.07-2.84) and OS (multivariate analyses: HR 2.03, 95% CI 1.31-3.14). The presence of EHS or MVI in ICI-treated HCC patients may not significantly impact the occurrence of any serious immune-related adverse events (irAEs) (grades ≥ 3) (EHS: OR 0.44, 95% CI 0.12-1.56; MVI: OR 0.68, 95% CI 0.24-1.88). CONCLUSION The presence of MVI or EHS in ICI-treated HCC patients may not significantly impact the occurrence of serious irAEs. However, the presence of MVI (but not EHS) in ICI-treated HCC patients may be a significant negative prognostic factor. Therefore, ICI-treated HCC patients with MVI warrant more attention.
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Affiliation(s)
- Cheng-Long Han
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Bao-Wen Tian
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Lun-Jie Yan
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Zi-Niu Ding
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Hui Liu
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Xin-Cheng Mao
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Jin-Cheng Tian
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Jun-Shuai Xue
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Si-Yu Tan
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Zhao-Ru Dong
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Yu-Chuan Yan
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Jian-Guo Hong
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Zhi-Qiang Chen
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Dong-Xu Wang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Tao Li
- Department of General Surgery, Qilu Hospital, The Second Hospital of Shandong University, 107 West Wen Hua Road, Jinan, 250012, People's Republic of China.
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Tian L, Tang S, Wang N, Deng H, Zhang Q, Shi T. Hepatic and portal vein Doppler ultrasounds in assessing liver inflammation and fibrosis in chronic HBV infection with a normal ALT level. Front Med (Lausanne) 2023; 10:1178944. [PMID: 37305137 PMCID: PMC10248231 DOI: 10.3389/fmed.2023.1178944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 05/08/2023] [Indexed: 06/13/2023] Open
Abstract
Aims To discuss the clinical value of hepatic and portal vein Doppler ultrasounds in assessing liver inflammation and fibrosis in patients with chronic hepatitis B virus (HBV) infection, and a normal alanine transaminase (ALT) level. Methods 94 patients with chronic HBV infections who had undergone ultrasound-guided liver biopsies were enrolled and grouped by the liver tissue pathological results. Analyzed the differences and correlation between parameters of the hepatic and portal vein Doppler ultrasounds are discussed across different degrees of liver inflammation and fibrosis. Results There were 27 patients with no significant liver damage and 67 patients with significant liver damage, there were significant differences in the parameters of the hepatic and portal vein Doppler ultrasounds between them (p < 0.05). As liver inflammation was aggravated, the inner diameter of the portal vein increased, and the blood flow velocities of the portal and superior mesenteric veins decreased (p < 0.05). When liver fibrosis became more severe, the inner diameter of the portal vein increased, while the blood flow velocities of the portal, superior mesenteric, and splenic veins decreased, and the Doppler waveforms of hepatic veins became unidirectional or flat (p < 0.05). The receiver operating characteristic (ROC) curve showed the assessment efficacy of hepatic and portal vein Doppler ultrasounds was superior to abdominal Doppler ultrasound alone in assessing liver fibrosis, and the combination of the two examination techniques outperformed any technique used alone. Conclusion The hepatic and portal vein Doppler ultrasounds have important clinical value for assessing liver fibrosis in patients with chronic HBV infection, to aid improve the diagnosis of liver fibrosis.
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Affiliation(s)
- Li Tian
- Department of Infectious Disease, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Shuyao Tang
- Department of Infectious Disease, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Na Wang
- Department of Infectious Disease, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Huan Deng
- Department of Infectious Disease, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Qunxia Zhang
- Department of Ultrasound Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Tongdong Shi
- Department of Infectious Disease, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Zhang J, Hu C, Xie X, Qi L, Li C, Li S. Immune Checkpoint Inhibitors in HBV-Caused Hepatocellular Carcinoma Therapy. Vaccines (Basel) 2023; 11:vaccines11030614. [PMID: 36992198 DOI: 10.3390/vaccines11030614] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 02/28/2023] [Accepted: 03/06/2023] [Indexed: 03/11/2023] Open
Abstract
Hepatitis B virus (HBV) infection is the main risk factor for the development of hepatocellular carcinoma (HCC), the most common type of liver cancer, with high incidence and mortality worldwide. Surgery, liver transplantation, and ablation therapies have been used to treat early HBV-caused HCC (HBV-HCC); meanwhile, in the advanced stage, chemoradiotherapy and drug-targeted therapy are regularly considered, but with limited efficacy. Recently, immunotherapies, such as tumor vaccine therapy, adoptive cell transfer therapy, and immune checkpoint inhibitor therapy, have demonstrated promising efficacy in cancer treatment. In particular, immune checkpoint inhibitors can successfully prevent tumors from achieving immune escape and promote an anti-tumor response, thereby boosting the therapeutic effect in HBV-HCC. However, the advantages of immune checkpoint inhibitors in the treatment of HBV-HCC remain to be exploited. Here, we describe the basic characteristics and development of HBV-HCC and introduce current treatment strategies for HBV-HCC. Of note, we review the principles of immune checkpoint molecules, such as programmed cell death protein 1(PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in HBV-HCC, as well as related inhibitors being considered in the clinic. We also discuss the benefits of immune checkpoint inhibitors in the treatment of HBV-HCC and the efficacy of those inhibitors in HCC with various etiologies, aiming to provide insights into the use of immune checkpoint inhibitors for the treatment of HBV-HCC.
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Affiliation(s)
- Jin Zhang
- School of Medicine, Chongqing University, Chongqing 400044, China
| | - Changwei Hu
- School of Medicine, Chongqing University, Chongqing 400044, China
| | - Xiaoxiao Xie
- School of Medicine, Chongqing University, Chongqing 400044, China
| | - Linzhi Qi
- School of Medicine, Chongqing University, Chongqing 400044, China
| | - Chuanzhou Li
- Department of Medical Genetics, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Shangze Li
- School of Medicine, Chongqing University, Chongqing 400044, China
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Extracellular vesicle-mediated immunoregulation in cancer. Int J Hematol 2022; 117:640-646. [PMID: 35951282 DOI: 10.1007/s12185-022-03436-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 07/29/2022] [Accepted: 07/31/2022] [Indexed: 10/15/2022]
Abstract
Extracellular vesicles (EVs) have emerged as immunomodulatory regulators during tumor progression. These small vesicles encapsulate a variety of molecules, including DNA, RNA, and proteins. When EVs come in contact with recipient cells, the EVs transmit various physiological characteristics; for example, proteins on the surface of EVs act as ligands. Immune checkpoint blockade targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA4), programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) has shown promise in a subset of cancer patients. PD-L1 on EVs acts as a key immunomodulator. Suppression of EV secretion enhances the efficacy of immunotherapy using immune checkpoint blockade antibodies. In addition to immune checkpoint blockade therapy, chimeric antigen receptor T (CAR-T) cell therapy has also been used to successfully eliminate cancer cells. Interestingly, CAR-T-cell-derived EVs express CAR on their surface. Compared with CAR-T cells, CAR-expressing EVs do not express PD1, so their antitumor effect cannot be weakened. In this review, we describe the current understanding of EVs in cancer immunity and summarize their crucial roles in immunomodulation.
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