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Background: Tumor vaccines for hepatocellular carcinoma (HCC) is an area of intense interest. Tremendous clinical trials have been conducted globally, but the efficacy and security of tumor vaccines are elusive. The aim of our study was to evaluate the efficacy and security of tumor vaccines. Methods: All relevant studies were identified in PubMed, EMBASE, Web of science and Cochrane Library databases. Objective response rate (ORR), median overall survival (OS), or median progression-free survival (PFS) and 95% CI were meta-analyzed based on the random-effects model. The individual-level data of OS, PFS were pooled by conducting survival analysis. All observed adverse events were collected. Results: 31 studies containing 35 eligible cohorts with 932 HCC patients were included. The pooled ORR were 7% (95% CI 3–14%), while ORR of dendritic cell (DC) vaccine (19%, 95% CI 11–29%) were highly significant than ORR of peptide vaccine (1%, 95% CI 0–5%). The pooled median OS and PFS were 13.67 months (95% CI 8.20–22.80) and 6.19 months (95% CI 2.97–12.91), respectively. The pooled median OS (DC vaccine: median OS = 21.77 months, 95% CI 18.33–25.86; Peptide vaccine: median OS = 10.08 months, 95% CI 5.23–19.44) and PFS (DC vaccine: median PFS = 11.01 months, 95% CI 5.25–23.09; Peptide vaccine: median PFS = 1.97 months, 95% CI 1.53–2.54) of DC vaccine were also longer than that of peptide vaccine. HBV-related HCC may acquire more benefits from tumor vaccines than HCV-related HCC. In almost all studies, the observed toxicities were moderate even tiny. Conclusions: Tumor vaccines for HCC, especially DC vaccine, are safe and worth exploring. More high-quality prospective studies are warranted. [ABSTRACT FROM AUTHOR]

Background and Aim: The role of hypoxia‐inducible factor‐1α (HIF‐1α) and hypoxia‐inducible factor‐2α (HIF‐2α) has been implicated in the clinical prognosis of hepatocellular carcinoma (HCC), but the results remain controversial. We aim to investigate the association of HIF‐1α and HIF‐2α overexpression with the prognosis and clinicopathological features of HCC. Methods: A systematic search was conducted in PubMed, Embase, Scopus, Web of Science, and Cochrane Library until June 20, 2020. Meta‐analysis was conducted to generate combined HRs with 95% confidence intervals (CI) for overall survival (OS) and disease‐free survival (DFS). Odds ratios (ORs) with 95% CI were also derived by fixed or random effect model. Results: Twenty‐two studies involving 3238 patients were included. Combined data suggested that overexpression of HIF‐1α in HCC was not only correlated with poorer OS [HR = 1.75 (95% CI: 1.53–2.00)] and DFS [HR = 1.64 (95% CI: 1.34–2.00)] but was also positively associated with vascular invasion [OR = 1.83 (95% CI: 1.36–2.48)], tumor size [OR = 1.36 (95% CI: 1.12–1.66)], and tumor number [1.74 (95% CI: 1.34–2.25)]. In contrast, HIF‐2α overexpression was not associated with the prognosis and clinicopathological features of HCC. Conclusion: Our data provided compelling evidence of a worse prognosis of HCC in HIF‐1α overexpression patients but not HIF‐2α overexpression ones. [ABSTRACT FROM AUTHOR]

• Hepatocellular carcinoma patients with impaired liver function have poor prognosis after receiving ICIs. • Both ALBI score and Child-Pugh score can stratify HCC patients. • ALBI score is simpler and more reliable for patient stratification than Child-Pugh score. • The incidence of adverse events is not significantly increased in impaired liver function patients. Most patients with hepatocellular carcinoma (HCC) have underlying cirrhosis and a compromised liver function. Immune checkpoint inhibitors (ICIs) have emerged as an important approach for HCC treatment. The purpose of our study was to explore the prognostic significance of liver function in HCC patients receiving ICIs. Hazard ratios (HR) with 95% confidence intervals (CI) were used to evaluate the relationship between liver function and overall survival (OS)/progression-free survival (PFS). 41 articles with 4483 patients with HCC were included. The pooled results revealed that either Child-Pugh score (OS:HR = 2.01,95 %CI:1.69–2.38; PFS:HR = 1.39,95 %CI:1.15–1.68) or albumin-bilirubin (ALBI) score (OS:HR = 2.04,95 %CI:1.55–2.69; PFS:HR = 1.42,95 %CI:1.21–1.67) can predict the patient prognosis. The Child-Pugh score has some degree of subjectivity, and the ALBI score can better stratify patients. Therefore, the ALBI score was used to evaluate patients' liver function and determine treatment options. Further subgroup analysis found that the results of prospective studies were statistically significant only for the ALBI score with regards to OS (HR = 1.69,95 %CI:1.26–2.26). Meanwhile, the effect of liver function on the efficacy of ICIs in the large-sample studies was not as obvious as that in small-sample studies. Moreover, the incidence of adverse events did not significantly increase in patients with impaired liver function. Poor liver function is associated with a poor prognosis in patients with HCC receiving ICIs. The ALBI score is simpler and reliable for patient stratification than the Child-Pugh score. Although the survival time of patients with impaired liver function may be relatively short, ICIs still have great potential for therapeutic applications. [ABSTRACT FROM AUTHOR]

• The RET gene, which is frequently mutated across many cancer types, has been proven to be involved in tumorigenesis. • However, its prediction of the therapeutic efficacy of immune checkpoint inhibitor (ICIs) therapy remains to be elucidated. • The present research aims to investigate the association between RET mutations and the efficiency of ICIs therapy. The RET gene, which is frequently mutated across many types of cancer, has been proven to be critically involved in tumorigenesis and tumour development; however, its prediction of the therapeutic efficacy of immune checkpoint inhibitor (ICI) therapy remains to be elucidated. The present research aims to investigate the association between RET mutations and the efficiency of ICI therapy. We analysed the role of RET mutations in predicting the prognosis of patients receiving ICIs therapy in the discovery cohort and validated it in the validation cohort. Then, multi-omics data from TCGA pan-cancer cohort was employed to propose the association between RET mutations and tumour inflamed anti-tumour immune response and tumour antigenicity. Our study revealed that among 606 cases and across five types of cancer, RET mutation was associated with better clinical outcomes for ICIs therapy, including elevated response rate, longer progression-free survival PFS, and longer overall survival OS. Multivariate analysis showed that RET mutation could independently predict the prognosis of patients treated with ICIs, after adjusting cancer types. The predictive value of RET status for the OS of patients treated with ICIs immunotherapy was further validated in the validation cohort (n = 1,409). Subgroup analysis suggested that only the monotherapy group showed significant differences in OS(P < 0.05) and PFS(P < 0.05) between RET -wildtype tumours and RET -mutant tumours. Multi-omics data analysis revealed potential anti-tumour immunity mechanisms of RET mutations, suggesting that RET -mutant tumours have enhanced immunogenicity, higher expression of immune checkpoints and chemokines, and higher immune cell infiltration than those observed in RET -wildtype tumours; thus, potentially indicating a more favourable response to immunotherapy. RET mutation may be a predictive biomarker of enhanced response to ICIs therapy. Extensive investigation of the underlying molecular mechanisms and prospective studies are needed in the future. [ABSTRACT FROM AUTHOR]