• DNA damage
• Nanosecond exposure to intense electric fields
• Pancreatic cancer
• Tumor ablation
• ceRNA hypotheses

• Mice
• Cell Line, Tumor
• Mice, Inbred C57BL
• Neoplasms, Experimental
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/pathology
• Pancreatic Neoplasms/therapy
• Electric Stimulation Therapy/methods
• Time Factors
• Cell Survival
• DNA Damage
• Gene Expression
• Animals

• bisphosphonate nanovaccines
• colorectal cancer liver metastases
• priming−boosting strategies
• radiofrequency ablations
• spatiotemporal heterogeneity

• Humans
• Nanovaccines
• Catheter Ablation
• Radiofrequency Ablation
• Adjuvants, Immunologic/pharmacology
• Adjuvants, Immunologic/therapeutic use
• Liver Neoplasms/drug therapy
• Cancer Vaccines/therapeutic use
• Diphosphonates/therapeutic use
• Colorectal Neoplasms/drug therapy

• PBMC
• immunosuppresion
• mass cytometry
• radiofrequency ablation
• recurrent hepatocellular carcinoma

• Humans
• Carcinoma, Hepatocellular/pathology
• Liver Neoplasms/pathology
• Leukocytes, Mononuclear
• Vascular Endothelial Growth Factor A
• Catheter Ablation
• Radiofrequency Ablation
• Immunosuppression Therapy
• Tumor Microenvironment

• Ablation
• Atezolizumab plus bevacizumab
• Cancer-free
• Curative conversion
• Hepatocellular carcinoma
• Resection
• Transarterial chemoembolization
• Treatment-free

• Humans
• Neoplasms
• Immunotherapy/methods
• Combined Modality Therapy
• Immunity
• Vaccination
• Tumor Microenvironment

• HCC
• ablation
• combination therapy
• immunotherapy
• tumor immune microenvironment

• advanced hepatocellular carcinoma
• apatinib
• camrelizumab
• combination therapeutic strategy
• microwave ablation

• Humans
• Carcinoma, Hepatocellular/drug therapy
• Liver Neoplasms/drug therapy
• Microwaves/adverse effects
• Retrospective Studies
• Vascular Endothelial Growth Factor A

Hepatocellular carcinoma (HCC) is an important cause of cancer death and is considered the 3rd most lethal around the world. Hepatectomy, liver transplantation, and ablation therapy are considered curative treatments for early-stage HCC. Transarterial chemoembolization is the preferred therapy for intermediate stage HCC. Ssystemic therapy is recommended for advanced HCC. For more than a decade, sorafenib and lenvatinib were used as the first-line treatment for the advanced HCC. For the great success of immunotherapy in melanoma and lung cancer, some immune-based treatments, such as immune checkpoint inhibitors (ICIs), have been applied in the treatment of HCC. The anti-programmed cell death protein 1 (PD1) antibodies, including nivolumab and pembrolizumab, have been approved by the Food and Drug Administration for sorafenib-pretreated patients. Moreover, due to the results of durable antitumor responses attained from the phase 3 trials, atezolizumab in combination with bevacizumab is now the standard therapy for advanced HCC. Recently, there are a lot of clinical trials involving the ICIs, as monotherapy or combination therapy, with tyrosine kinase inhibitors, antiangiogenic drugs, cytotoxic agents, and locoregional treatments, providing a promising outcome for advanced HCC. Thus, this review summarized the role of ICIs for HCC patients with monotherapy or combination therapy. The success and failures of monotherapy and combination therapy involving ICIs have provided advanced insights into HCC treatment and led to novel avenues to improve therapy efficacy in HCC.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide and is increasing in incidence. Local ablative therapy plays a leading role in HCC treatment. Radiofrequency (RFA) is one of the first-line therapies for early local ablation. Other local ablation techniques (e.g., microwave ablation, cryoablation, irreversible electroporation, phototherapy.) have been extensively explored in clinical trials or cell/animal studies but have not yet been established as a standard treatment or applied clinically. On the one hand, single treatment may not meet the needs. On the other hand, ablative therapy can stimulate local and systemic immune effects. The combination strategy of immunotherapy and ablation is reasonable. In this review, we briefly summarized the current status and progress of ablation and immunotherapy for HCC. The immune effects of local ablation and the strategies of combination therapy, especially synergistic strategies based on biomedical materials, were discussed. This review is hoped to provide references for future researches on ablative immunotherapy to arrive to a promising new era of HCC treatment.

• ablation
• hepatocellular carcinoma
• immunotherapy
• multifunctional nanoplatform
• nanomedicine
• synergistic therapy

The incidence of hepatocellular carcinoma (HCC) is rising worldwide, and there is limited therapeutic efficacy due to tumor microenvironment heterogeneity and difficulty in early-stage screening. This study aimed to develop and validate a gene set-based signature for early-stage HCC (eHCC) patients and further explored specific marker dysregulation mechanisms as well as immune characteristics.

We performed an integrated bioinformatics analysis of genomic, transcriptomic, and clinical data with three independent cohorts. We systematically reviewed the crosstalk between specific genes, tumor prognosis, immune characteristics, and biological function in the different pathological stage samples. Univariate and multivariate survival analyses were performed in The Cancer Genome Atlas (TCGA) patients with survival data. Diethylnitrosamine (DEN)-induced HCC in Wistar rats was employed to verify the reliability of the predictions.

We identified a Cluster gene that potentially segregates patients with eHCC from non-tumor, through integrated analysis of expression, overall survival, immune cell characteristics, and biology function landscapes. Immune infiltration analysis showed that lower infiltration of specific immune cells may be responsible for significantly worse prognosis in HCC (hazard ratio, 1.691; 95% CI: 1.171–2.441; p = 0.012), such as CD8 Tem and cytotoxic T cells (CTLs) in eHCC. Our results identified that Cluster C1 signature presented a high accuracy in predicting CD8 Tem and CTL immune cells (receiver operating characteristic (ROC) = 0.647) and cancerization (ROC = 0.946) in liver. As a central member of Cluster C1, overexpressed PRKDC was associated with the higher genetic alteration in eHCC than advanced-stage HCC (aHCC), which was also connected to immune cell-related poor prognosis. Finally, the predictive outcome of Cluster C1 and PRKDC alteration in DEN-induced eHCC rats was also confirmed.

As a tumor prognosis-relevant gene set-based signature, Cluster C1 showed an effective approach to predict cancerization of eHCC and its related immune characteristics with considerable clinical value.

• PRKDC
• early-stage hepatocellular carcinoma (eHCC)
• gene-set signature
• immune cells
• prognosis

• Hepatocellular carcinoma
• Immunotherapy
• Liver-directed therapy
• PD-1

Hepatocellular carcinoma (HCC) is one of most common cancers that cause death in the world. Thermal ablation (TA) is an important alternative treatment method for HCC patients who are not appropriate for surgery or liver transplantation. Particularly for small and early HCCs, TA can be considered as the first-line curative treatment. However, local and distant recurrence rates are still high even though the TA equipment and technology develop rapidly. Immunotherapy is a novel systemic treatment method to enhance the anti-tumor immune response of HCC patients, which has the potential to reduce the tumor recurrence and metastasis. The combination of local TA and systemic immunotherapy for HCCs may be an ideal treatment for enhancing the efficacy of TA and controlling the recurrence. Herein we summarize the latest progress in TA, immunotherapy, and their combination for the treatment of patients with HCC and discuss the limitations and future research directions of the combined therapy.

• Hepatocellular carcinoma
• Thermal ablation
• Radiofrequency ablation
• Immunotherapy
• Recurrence
• Anti-tumor immune response

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortalities worldwide. Patients with early-stage HCC are eligible for curative treatments, such as surgical resection, liver transplantation (LT) and percutaneous ablation. Although curative treatments provide excellent long-term survival, almost 70–80% of patients experience HCC recurrence after curative treatments. Tumor-related factors, including tumor size, number and differentiation, and underlying liver disease, are well-known risk factors for recurrence following curative therapies. Moreover, the tumor microenvironment (TME) also plays a key role in the recurrence of HCC. Many immunosuppressive mechanisms, such as an increase in regulatory T cells and myeloid-derived suppressor cells with a decrease in cytotoxic T cells, are implicated in HCC recurrence. These suppressive TMEs are also modulated by several factors and pathways, including mammalian target of rapamycin signaling, vascular endothelial growth factor, programmed cell death protein 1 and its ligand 1. Based on these mechanisms and the promising results of immune checkpoint blockers (ICBs) in advanced HCC, there have been several ongoing adjuvant studies using a single or combination of ICB following curative treatments in HCC. In this review, we strive to provide biologic and immunological markers, prognostic factors, and challenges associated with clinical outcomes after curative treatments, including resection, LT and ablation.

• ablation
• hepatocellular carcinoma
• immune checkpoint blockers
• immune suppression
• liver transplantation
• outcomes
• recurrence
• resection
• tumor microenvironment

Hepatocellular carcinoma (HCC) is a common cause of cancer-related deaths worldwide. Unlike other types of cancer, HCC can be treated with locoregional treatments (LRTs) such as radiofrequency ablation (RFA) or transarterial chemoembolization (TACE). However, recurrences following LRTs are common, and strategies to improve long-term outcomes need to be developed. The exhaustion of anti-tumor immunity in HCC has been well established in many reports and the immunomodulatory effects of LRTs (enhancement of tumor antigen-specific T cell responses after RFA, reduction of effector regulatory T cells after TACE) have also been reported in several previous studies. However, a comprehensive review of previous studies and the possible roles of immunotherapy following LRTs in HCC are not known. In this review, we discuss the immunological evidence of current clinical trials using LRTs and combined immunotherapies, and the possible role of this strategy.

• HCC
• adjuvant treatment
• immunotherapy
• locoregional treatment

• antineoplastic protocols
• guidelines as topic
• immunotherapy
• liver neoplasms

• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/pathology
• Guidelines as Topic
• Humans
• Immunotherapy/methods
• Liver Neoplasms/drug therapy
• Liver Neoplasms/pathology

• immunotherapy
• liver cancer
• real-world
• systemic treatment
• unresectable hepatocellular carcinoma

• Immunotherapy
• immunomodulation
• interventional therapy
• tumor

Lung cancer is the leading cause of cancer death worldwide, with approximately 1.6 million cancer related deaths each year. Prognosis is best in patients with early stage disease, though even then five-year survival is only 55% in some groups. Median survival for advanced non-small cell lung cancer (NSCLC) is 8–12 months with conventional treatment. Immune checkpoint inhibitor (ICI) therapy has revolutionised the treatment of NSCLC with significant long-term improvements in survival demonstrated in some patients with advanced NSCLC. However, only a small proportion of patients respond to ICI, suggesting the need for further techniques to harness the potential of ICI therapy. Thermal ablation utilizes the extremes of temperature to cause tumour destruction. Commonly used modalities are radiofrequency ablation (RFA), cryoablation and microwave ablation (MWA). At present thermal ablation is reserved for curative-intent therapy in patients with localized NSCLC who are unable to undergo surgical resection or stereotactic ablative body radiotherapy (SABR). Limited evidence suggests that thermal ablative modalities can upregulate an anticancer immune response in NSCLC. It is postulated that thermal ablation can increase tumour antigen release, which would initiate and upregulated steps in the cancer immunity cycle required to elicit an anticancer immune response. This article will review the current thermal ablative techniques and their ability to modulate an anti-cancer immune response with a view of using thermal ablation in conjunction with ICI therapy.

• Non-small cell lung cancer (NSCLC)
• cancer immunity
• immunotherapy
• thermal ablation

Hepatocellular carcinoma (HCC) is among the most common cancer diseases worldwide and has only limited treatment options at advanced disease stages. Activation of the immune system with checkpoint inhibitors has revolutionized cancer medicine and has become important also for HCC treatment. Here, we summarize the current status of immunotherapy options for HCC and highlight how combination with locoregional therapies could improve the outcome of patients. Novel pathways and targets for immunologic drug development are briefly discussed that could help to increase the response rate of these approaches in HCC.

Background: Hepatocellular carcinoma (HCC) still represents a human tumor entity with very limited therapeutic options, especially for advanced stages. Here, immune checkpoint modulating drugs alone or in combination with local ablative techniques could open a new and attractive therapeutic “door” to improve outcome and response rate for patients with HCC. Methods: Published data on HCC experimental to pre-(clinical) treatment strategies from standard of care to novel immunomodulatory concepts were summarized and discussed in detail. Results: Overall, our knowledge of the role of immune checkpoints in HCC is dramatically increased in the last years. Experimental and pre-clinical findings could be translated to phase 1 and 2 clinical trials and became standard of care. Local ablative techniques of HCC could improve the effectivity of immune checkpoint inhibitors in situ. Conclusions: This review demonstrates the importance of immunomodulatory treatment strategies of HCC, whereby the “best treatment code” of immune checkpoint drugs, combination with ablative techniques and of timing must be evaluated in coming clinical trials.

• hepatocellular carcinoma
• immune checkpoint inhibitors
• immunotherapy
• locoregional treatment

• combination therapies
• hepatocellular carcinoma
• immunotherapy
• therapy resistance
• translational approaches

In advanced-stage hepatocellular carcinoma (HCC), systemic treatment represents the standard therapy. Target therapy has marked a new era based on a greater knowledge of molecular disease signaling. Nonetheless, survival outcomes and long-term response remain unsatisfactory, mostly because of the onset of primary or acquired resistance. More recently, results from clinical trials with immune targeting agents, such as the immune checkpoint inhibitors (ICIs), have shown a promising role for these drugs in the treatment of advanced HCC. In the context of an intrinsic tolerogenic liver environment, since HCC-induced immune tolerance, it is supported by multiple immunosuppressive mechanisms and several clinical trials are now underway to evaluate ICI-based combinations, including their associations with antiangiogenic agents or multikinase kinase inhibitors and multiple ICIs combinations. In this review, we will first discuss the basic principles of hepatic immunogenic tolerance and the evasive mechanism of antitumor immunity in HCC; furthermore we will elucidate the consistent biological rationale for immunotherapy in HCC even in the presence of an intrinsic tolerogenic environment. Subsequently, we will critically report and discuss current literature on ICIs in the treatment of advanced HCC, including a focus on the currently explored combinatorial strategies and their rationales. Finally, we will consider both challenges and future directions in this field.

• combinatorial immunotherapy strategies
• hepatocellular carcinoma
• immune checkpoint inhibitors
• liver tolerance

• HCC
• MWA
• RFA
• ablation
• immunomodulation
• liver

• Carcinoma, Hepatocellular/therapy
• Clinical Trials as Topic
• Combined Modality Therapy
• Humans
• Immunotherapy/methods
• Liver Neoplasms/therapy
• Microwaves/therapeutic use
• Neoplasm Recurrence, Local
• Radiofrequency Ablation/methods
• Treatment Outcome

• 2019 Dotation Agir pour les Maladies Chroniques

Locoregional therapies (LRTs) including radiofrequency ablation, surgical resection, and TACE, play a pivotal role in the treatment of early stage/locally advanced hepatocellular carcinoma (HCC). Besides their direct effect on tumor cells, LRTs also play an essential role in the immunomodulation of the tumor microenvironment which is of interest in the current era of cancer immunotherapy. In this review, we describe the HCC immune microenvironment and how it is affected by LRTs as described in multiple pre-clinical and clinical studies and provide the rationale for combining LRTs with immunotherapy.

• hepatocellular carcinoma
• immunotherapy
• locoregional therapies

Adoptive cellular immunotherapy (ACI) is a promising treatment for a number of cancers. Cytokine-induced killer cells (CIKs) are considered to be major cytotoxic immunologic effector cells. Usually cancer cells are able to suppress antitumor responses by secreting immunosuppressive factors. CIKs have significant antitumor activity and are capable of eradicating tumors with few side effects. They are a very encouraging cell population used against hematological and solid tumors, with an inexpensive expansion protocol which could yield to superior clinical outcome in clinical trials employing adoptive cellular therapy combination. In the last decade, clinical protocols have been modified by enriching lymphocytes with CIK cells. They are a subpopulation of lymphocytes characterized by the expression of CD3+ and CD56+ wich are surface markers common to T lymphocytes and natural killer NK cells. CIK cells are mainly used in two diseases: in hematological patients who suffer relapse after allogeneic transplantation and in patients with hepatic carcinoma after surgical ablation to eliminate residual tumor cells. Dendritic cells DCs could play a pivotal role in enhancing the antitumor efficacy of CIKs.

• Cytokine-induced killer cells
• Dendritic cells
• adoptive cellular immunotherapy

Hepatocellular carcinoma (HCC) arises on the background of chronic liver disease. Despite the development of effective anti-viral therapeutics HCC is continuing to rise, in part driven by the epidemic of non-alcoholic fatty liver disease. Many patients present with advanced disease out with the criteria for transplant, resection or even locoregional therapy. Currently available therapeutics for HCC are effective in a small minority of individuals. However, there has been a major global interest in immunotherapies for cancer and although HCC has lagged behind other cancers, great opportunities now exist for treating HCC with newer and more sophisticated agents. Whilst checkpoint inhibitors are at the forefront of this revolution, other therapeutics such as inhibitory cytokine blockade, oncolytic viruses, adoptive cellular therapies and vaccines are emerging. Broadly these may be categorized as either boosting existing immune response or stimulating de novo immune response. Although some of these agents have shown promising results as monotherapy in early phase trials it may well be that their future role will be as combination therapy, either in combination with one another or in combination with treatment modalities such as locoregional therapy. Together these agents are likely to generate new and exciting opportunities for treating HCC, which are summarized in this review.

• Adoptive cell therapy
• Cancer vaccine
• Checkpoint inhibitor
• Hepatocellular carcinoma
• Immunotherapy
• Liver cancer
• Oncolytic virus

• Antineoplastic Agents, Immunological/therapeutic use
• Cancer Vaccines/therapeutic use
• Carcinoma, Hepatocellular/immunology
• Carcinoma, Hepatocellular/therapy
• Clinical Trials as Topic
• Combined Modality Therapy/methods
• Combined Modality Therapy/trends
• Humans
• Immunotherapy/methods
• Immunotherapy/trends
• Liver Neoplasms/immunology
• Liver Neoplasms/therapy
• Oncolytic Virotherapy/methods
• Oncolytic Virotherapy/trends
• Treatment Outcome

Hepatocellular carcinoma (HCC) is a highly aggressive malignant disease, with a poor clinical prognosis. Many standard therapies are often considered for HCC treatment today; however, these conventional therapies often fail to achieve sufficiently effective clinical results. Today, HCC therapy is set to undergo a major revolution, owing to rapid developments in cancer immunotherapy, particularly immune checkpoint inhibitor therapy. Cancer immunotherapy is a novel and promising treatment strategy that differs significantly from conventional therapies in its approach to achieve antitumor effects. In fact, many cancer immunotherapies have been tested worldwide and shown to be effective against various types of cancer; HCC is no exception to this trend. For example, we identified a specific cancer antigen called glypican-3 (GPC3) and performed clinical trials of GPC3-targeted peptide vaccine immunotherapy in patients with HCC. Here, we present an overview of the immune mechanisms for development and progression of HCC, our GPC3-based immunotherapy, and immune checkpoint inhibitor therapy against HCC. Finally, we discuss the future prospects of cancer immunotherapy against HCC. We believe that this review and discussion of cancer immunotherapy against HCC could stimulate more interest in this promising strategy for cancer therapy and help in its further development.

• Hepatocellular carcinoma
• Cancer immunotherapy
• Immune checkpoint inhibitor
• Glypican-3
• Cancer vaccine
• Clinical trials
• Cytotoxic T-lymphocytes

• Combinatorial immunotherapy strategies
• Hepatitis B virus
• Hepatocellular carcinoma
• Immune checkpoint inhibitors
• Underlying liver disease

• Antineoplastic Agents, Immunological/therapeutic use
• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/immunology
• China
• Clinical Protocols
• Clinical Trials as Topic
• Humans
• Immunotherapy/methods
• Liver Neoplasms/drug therapy
• Liver Neoplasms/immunology

• Checkpoint inhibitors
• Hepatocellular carcinoma
• Immunotherapy
• Ligand programmed death-ligand-1
• Programmed cell death protein-1

Ablation, as a minimally invasive therapy for solid tumors, has been widely used in clinical practice and achieved satisfactory outcome. Tumor ablation has an effect on the tumor microenvironment so that a good environment for tumor specific immune recognition can be provided. Thus, combined immunotherapy can enhance the antitumor immune effect and improve the long-term outcome. The effect of tumor ablation on the immune function of the body and the combination of immunotherapy have become a hot topic in recent years. In this article, we will summarize the related clinical studies and comments on the effect of ablation of solid tumors on immune function and the status of combined immunotherapy.

• Tumor ablation
• Immunotherapy
• Immune effect
• Tumor microenvironment

• Interventional oncology
• Liver tumor treatment
• Minimally invasive oncology
• Percutaneous tumor treatment
• Radiofrequency ablation

• Cellular targets
• Combinational therapy
• Hepatocellular carcinoma
• Immunostimulation
• Immunotherapy
• Molecular targets
• Virotherapy

• CTLA-4 inhibitor
• PD-1 inhibitor
• RFA
• TACE
• check point inhibitors
• hepatocellular carcinoma
• immune tharapy
• radiofrequency ablation
• transcatheter arterial chemoembolization

• colorectal liver metastases
• microwave ablation
• transcatheter arterial chemoembolization

• Cancer
• Hepatocellular carcinoma (HCC)
• Immunotherapy
• Integration
• Radiofrequency ablation (RFA)

The recurrence rates of Hepatocellular carcinoma (HCC) are high, necessitating novel and effective adjuvant therapies. Therefore, we conducted a phase II study of glypican-3 (GPC3) peptide vaccine as an adjuvant therapy for HCC patients. Forty-one patients with initial HCC who had undergone surgery or radiofrequency ablation (RFA) were analyzed in this phase II, open-label, single-arm trial. Ten vaccinations were performed for 1 y after curative treatment. We also investigated case-control subjects, where selected patients treated surgically during the same period were analyzed. The expression of GPC3 in the available primary tumors was determined by immunohistochemical analysis. Six patients received RFA therapy while 35 received surgery. The recurrence rate tended to be lower in the 35 patients treated with surgery plus vaccination compared to 33 patients who underwent surgery alone (28.6% vs. 54.3% and 39.4% vs. 54.5% at 1 and 2 y, respectively; p = 0.346, 0.983). Twenty-five patients treated with surgery and vaccination had GPC3-positive tumors; the recurrence rate in this group was significantly lower compared to that in 21 GPC3-positive patients who received surgery only (24% vs. 48% and 52.4% vs. 61.9% at 1 and 2 y, respectively; p = 0.047, 0.387). The GPC3 peptide vaccine improved the 1-y recurrence rate in patients with GPC3-positive tumors. This study demonstrated that GPC3 expression by the primary tumor may be used as a biomarker in a putative larger randomized clinical trial to determine the efficacy of the GPC3-derived peptide vaccine.

• Adjuvant therapy
• CTL
• HCC
• glypican-3
• peptide vaccine

• Dendritic cell vaccination
• Dendritic cells
• Hepatocellular carcinoma
• Immunotherapy
• Therapy

• Cancer Vaccines/therapeutic use
• Carcinoma, Hepatocellular/immunology
• Carcinoma, Hepatocellular/therapy
• Dendritic Cells/immunology
• Humans
• Immunotherapy/methods
• Immunotherapy/trends
• Liver Neoplasms/immunology
• Liver Neoplasms/therapy

Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is the fifth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence, treatment options remain limited for advanced HCC, and as a result prognosis continues to be poor. Current therapeutic options, surgery, chemotherapy and radiotherapy, have only modest efficacy. New treatment modalities to prolong survival and to minimize the risk of adverse response are desperately needed for patients with advanced HCC. Tumor immunotherapy is a promising, novel treatment strategy that may lead to improvements in both treatment-associated toxicity and outcome. The strategies have developed in part through genomic studies that have yielded candidate target molecules and in part through basic biology studies that have defined the pathways and cell types regulating immune response. Here, we summarize the various types of HCC immunotherapy and argue that the newfound field of HCC immunotherapy might provide critical advantages in the effort to improve prognosis of patients with advanced HCC. Already several immunotherapies, such as tumor-associated antigen therapy, immune checkpoint inhibitors and cell transfer immunotherapy, have demonstrated safety and feasibility in HCC patients. Unfortunately, immunotherapy currently has low efficacy in advanced stage HCC patients; overcoming this challenge will place immunotherapy at the forefront of HCC treatment, possibly in the near future.

• Cell transfer immunotherapy
• Cytokine therapy
• Hepatocellular carcinoma
• Immune checkpoint inhibitors
• Immunotherapy
• Tumor-associated antigens therapy

• Animals
• Antineoplastic Agents/therapeutic use
• Carcinoma, Hepatocellular/immunology
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/therapy
• Cytokines/therapeutic use
• Humans
• Immunotherapy/methods
• Immunotherapy, Adoptive
• Liver Neoplasms/immunology
• Liver Neoplasms/pathology
• Liver Neoplasms/therapy
• Molecular Targeted Therapy
• Treatment Outcome

Hepatocellular cancer is the 5^th most common cancer in the world and the third cause of death by malignant disease. Locoregional therapies are the most usual treatment of choice for patients with early or intermediate stage of disease. The main diagnostic tools for the detection of recurrence are the radiological techniques such as 4-phase computed tomography or dynamic contrast enhanced magnetic resonance imaging. However, in order to achieve best evaluation of treatment outcome and recurrence rates, there is a great need for the identification of specific and easily measured circulating biomarkers. The aim of this review is to analyze the existing data considering the prognostic significance of changes of serum diagnostic markers such as alpha-fetoprotein, des-gamma-carboxy prothrombin, alpha-fetoprotein-L3, angiogenetic factors (vascular endothelial growth factor, hypoxia inducible factor-1a) and immune parameters before and after radiofrequency ablation or transarterial chemoembolization.

• Radiofrequency ablation
• Transarterial chemoembolization
• Hepatocellular cancer
• Circulating biomarkers
• Prognosis

Hepatocellular carcinoma is a highly aggressive malignancy and is the third leading cause of cancer-related deaths worldwide. Although surgery is currently considered the most effective curative treatment for this type of cancer, it is note that most of patients have a poor prognosis due to chemioresistence and tumor recurrence. Loco-regional therapies, including radiofrequency ablation, surgical resection and transcatheter arterial chemoembolization play a major role in the clinical management of hepatocellular carcinoma. In order to improve the treatment outcome of patients diagnosed with this disease, several in vivo studies by using different techniques on cancer mouse models have been performed. This review will focus on the latest papers on the efficacy of loco-regional therapy and combined treatments in patients and mouse models of hepatocellular carcinoma.

• Drug delivery
• Efficacy
• Hepatocellular carcinoma
• Loco-regional treatments
• Safety

• Aspartate-β-hydroxylase
• Epitope
• Hepatocellular carcinoma
• Immunotherapy
• T cells

• Liver cancer
• quality of life
• radiofrequency ablation (RFA)
• survival period
• transcatheter arterial chemoembolization (TACE)

• cancer vaccines
• glypican 3
• antibody treatment
• vaccinia
• oncolytic virus

• CTLA-4 Antigen/antagonists & inhibitors
• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/immunology
• Carcinoma, Hepatocellular/pathology
• Granulocyte-Macrophage Colony-Stimulating Factor/biosynthesis
• Granulocyte-Macrophage Colony-Stimulating Factor/genetics
• Humans
• Immunity, Innate
• Immunotherapy
• Inflammation/complications
• Inflammation/drug therapy
• Inflammation/pathology
• Liver Neoplasms/drug therapy
• Liver Neoplasms/immunology
• Liver Neoplasms/pathology
• Oncolytic Viruses
• Tumor Microenvironment/immunology

• ZIA BC011258-03 Intramural NIH HHS
• ZIA BC011343-01 Intramural NIH HHS
• ZIA BC011344-02 Intramural NIH HHS
• ZIA BC011344-01 Intramural NIH HHS
• ZIA BC011258-01 Intramural NIH HHS
• ZIA BC011343-02 Intramural NIH HHS
• ZIA BC011258-02 Intramural NIH HHS
• ZIA BC011258 Intramural NIH HHS
• ZIA BC011344 Intramural NIH HHS
• ZIA BC011343-03 Intramural NIH HHS