Is Adjuvant Cellular Immunotherapy Essential after TACE-Predominant Minimally-Invasive Treatment for Hepatocellular Carcinoma? A Systematic Meta-Analysis of Studies Including 1774 Patients

Ding, Min; Wang, Ying; Chi, Jiachang; Tang, Xiaodong; Cui, Dan; Qian, Qijun; Zhai, Bo

doi:10.1371/journal.pone.0168798

Cited by 22 publications

(15 citation statements)

References 29 publications

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“…Moreover, in contrast to those previous systematic reviews [20,21], our data found adjuvant AIT significantly reduced the rate of mortality and tumor recurrence for such patients. Our results were confirmed by other meta-analysis that AIT was a feasible adjuvant treatment for the improvement of the clinical outcomes for HCC patients after minimally invasive treatment [46]. …”

Section: Discussionsupporting

confidence: 87%

Timely meta-analysis on the efficacy of adoptive immunotherapy for hepatocellular carcinoma patients after curative therapy

Liao

You

et al. 2017

PLoS ONE

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AimsThe role of adoptive immunotherapy (AIT) for patients with hepatocellular carcinoma (HCC) who have received curative therapy is still not well illustrated. This timely meta-analysis aims to update the current evidence on efficacy and safety of AIT for patients with HCC who have received curative therapy.MethodsWe searched PubMed, EMBASE, Scopus and the Cochrane Library Through January 2017 for relevant studies. Mortality and tumor recurrence were compared between patients with or without adjuvant AIT. The meta-analysis was performed using Review Manager 5.3.ResultsEight studies involving 1861 patients met the eligibility criteria and were meta-analyzed. Adjuvant AIT was associated with significantly lower mortality at 1 year (RR 0.64, 95%CI 0.52–0.79), 3 years (RR 0.73, 95%CI 0.65–0.81) and 5 years (RR 0.86, 95%CI 0.79–0.94). Similarly, adjuvant AIT was associated with significantly lower recurrence rate than curative therapies alone at 1 year (RR 0.64, 95%CI 0.49–0.82), 3 years (RR 0.85, 95%CI 0.79–0.91) and 5 years (RR 0.90, 95%CI 0.85–0.95). Short-term outcomes were confirmed in sensitivity analyses based on randomized trials or choice of random- or fixed-effect meta-analysis model. None of the included patients experienced grade 4 adverse events.ConclusionsThis timely meta-analysis confirms the evidence that adjuvant AIT for patients with HCC after curative treatment lowers risk of mortality and tumor recurrence.

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Section: Discussionsupporting

confidence: 87%

Timely meta-analysis on the efficacy of adoptive immunotherapy for hepatocellular carcinoma patients after curative therapy

Liao

You

et al. 2017

PLoS ONE

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“…In light of previous studies, mitochondrial oxidative stress is regarded as the dominant cellular event in APAP-induced acute hepatotoxicity (Wang et al., 2016a; Yan et al., 2018). Several natural compounds have been reported to protect against APAP-induced acute liver injury via antioxidant capacity (Rasool et al., 2010; Ding et al., 2016; Rashid et al., 2016). In our study, tempol treatment upregulated levels of antioxidant proteins, including SOD, catalase and GSH, thus inhibiting oxidative stress in APAP-induced liver injury.…”

Section: Discussionmentioning

confidence: 99%

Tempol Protects Against Acetaminophen Induced Acute Hepatotoxicity by Inhibiting Oxidative Stress and Apoptosis

Wang

Zhang

et al. 2019

Front. Physiol.

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Acetaminophen (APAP)-induced acute hepatotoxicity is the leading cause of drug-induced acute liver failure. The aim of this study was to evaluate the effects of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol) on the protection of APAP-induced hepatotoxicity in mice. Mice were pretreated with a single dose of tempol (20 mg/kg per day) orally for 7 days. On the seventh day, mice were injected with a single dose of APAP (300 mg/kg) to induce acute hepatotoxicity. Our results showed that tempol treatment markedly improved liver functions with alleviations of histopathological damage induced by APAP. Tempol treatment upregulated levels of antioxidant proteins, including superoxide dismutase, catalase, and glutathione. Also, phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) and protein expression of nuclear factor erythroid 2-related factor (Nrf 2) and heme oxygense-1 (HO-1) were all increased by tempol, which indicated tempol protected against APAP-induced hepatotoxicity via the PI3K/Akt/Nrf2 pathway. Moreover, tempol treatment decreased pro-apoptotic protein expressions (cleaved caspase-3 and Bax) and increased anti-apoptotic Bcl-2 in liver, as well as reducing apoptotic cells of TUNEL staining, which suggested apoptotic effects of tempol treatment. Overall, we found that tempol normalizes liver function in APAP-induced acute hepatotoxicity mice via activating PI3K/Akt/Nrf2 pathway, thus enhancing antioxidant response and inhibiting hepatic apoptosis.

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“…The results verified that vaccination of mice with the novel HSP70-P/AFP-P vaccine mounted strong natural killer cell and CD8 + T cell responses, inducing a protective effect against AFP-producing tumors in mice [ 68 ]. A systemic meta-analysis indicated that cellular immunotherapy was a feasible adjuvant treatment that could be beneficial for the improvement of short-term response and long-term survival of HCC patients after minimally invasive treatment [ 76 ]. Recently, clinical trials showed that nivolumab, a programmed cell death protein-1 (PD-1) immune checkpoint inhibitor, produced durable objective responses for treatment of HCC, indicating the possibility of combining nivolumab with AFP to suppress the proliferation of cancer cells [ 77 ].…”

Section: Application Of Afp In the Immunotherapy Of Hepatocellularmentioning

confidence: 99%

Alpha-Fetoprotein and Hepatocellular Carcinoma Immunity

Wang

2018

Canadian Journal of Gastroenterology and Hepatology

114

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Hepatocarcinoma is one of the most prevalent gastroenterological cancers in the world with less effective therapy. As an oncofetal antigen and diagnostic marker for liver cancer, alpha-fetoprotein (AFP) possesses a variety of biological functions. Except for its diagnosis in liver cancer, AFP has become a target for liver cancer immunotherapy. Although the immunogenicity of AFP is weak and it could induce the immune escapes through inhibiting the function of dendritic cells, natural killer cells, and T lymphocytes, AFP has attracted more attention in liver cancer immunotherapy. By in vitro modification, the immunogenicity and immune response of AFP could be enhanced. AFP-modified immune cell vaccine or peptide vaccine has displayed the specific antitumor immunity against AFP-positive tumor cells and laid a better foundation for the immunotherapy of liver cancer.

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Is Adjuvant Cellular Immunotherapy Essential after TACE-Predominant Minimally-Invasive Treatment for Hepatocellular Carcinoma? A Systematic Meta-Analysis of Studies Including 1774 Patients

Cited by 22 publications

References 29 publications

Timely meta-analysis on the efficacy of adoptive immunotherapy for hepatocellular carcinoma patients after curative therapy

Timely meta-analysis on the efficacy of adoptive immunotherapy for hepatocellular carcinoma patients after curative therapy

Tempol Protects Against Acetaminophen Induced Acute Hepatotoxicity by Inhibiting Oxidative Stress and Apoptosis

Alpha-Fetoprotein and Hepatocellular Carcinoma Immunity

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