Radiofrequency ablation for the treatment of HCC – Maybe much more than simple tumor destruction?

COMMENTARY ONRadiofrequency thermal ablation for hepatocellular carcinoma stimulates autologous NK-cell response. Zerbini A, Pilli M, Laccabue D, Pelosi G, Molinari A, Negri E, Cerioni S, Fagnoni F, Soliani P, Ferrari C, Missale G. Gastroenterology, 2010 May;138(5):1931–1942. Eup 2010 Jan 11. Copyright 2010. Abstract reprinted with permission from Elsevier Inc.www.ncbi.nlm.gov/pubmed/20060829Abstract: Background & AimsRadiofrequency thermal ablation (RFA) is a minimally invasive technique used as standard local therapy of hepatocellular carcinoma and second-line treatment for metastatic liver tumors. Studies in preclinical models and in patients have shown that thermal destruction of tumor tissue can enhance anti-tumor cellular responses, but our knowledge of its impact on natural killer (NK) cells is still very limited.MethodsThirty-seven patients undergoing RFA for hepatocellular carcinoma were studied for peripheral blood lymphocytes counts followed by phenotypic and functional characterization of NK-cell population.ResultsPeripheral blood lymphocytes kinetics revealed an increased frequency and absolute number of NK-cells expressing higher levels of activatory along with reduced levels of inhibitory NK receptors, and increased functional NK-cell activity. A prevalent expansion of the CD3(−)CD56(dim) NK subset was observed compared to the CD3(−)CD56(bright) counterpart. Interferon-gamma production, anti-K562 cell-cytotoxicity, and antibody-dependent cell-cytotoxicity, appeared consistently increased in terms of both absolute activity and killing efficiency at 4weeks after RFA, as compared to baseline. Interestingly, when recurrence-free survival was assessed in two groups of patients separated according to higher vs lower enhancement of cytotoxicity and/or interferon-gamma production, a significant difference was observed, thus suggesting a potential predictive role of NK functional assays on efficacy of RFA.ConclusionsRFA can lead to stimulation of NK-cells with a more differentiated and proactivatory phenotypic profile with general increase of functional activities. This observation may be relevant for development of adjuvant immunotherapeutic strategies aimed at enhancing NK-cell responses against primary and metastatic liver tumors. Copyright 2010 AGA Institute

Targets for immunotherapy of liver cancer

Drug development in hepatocellular carcinoma (HCC) has been characterised by many failures in the past. Despite good rationales and promising phase II data, many phase III trials failed. Immunotherapy represents an alternative treatment approach that has been successful in many different cancer types. As an inflammation induced cancer, HCC represents a very interesting target for immune based approaches. Indeed, early results from clinical trials testing immune checkpoint inhibitors are not only promising, but have already led to evaluation in a phase III setting. Herein, we summarise our current knowledge on the rationale, mechanism of action and clinical data for immune checkpoint blockade in HCC. In addition, we provide an overview of other novel immune based approaches currently under development for the treatment of HCC, such as adoptive cell based and antibody-based approaches

Locally Advanced Cancer of the Esophagus, Current Treatment Strategies, and Future Directions

For patients with locally advanced esophageal cancer no clear standard of care exists. Notwithstanding several negative phase III studies the data provide support for so-called trimodality treatment and this is probably the most common approach. Even the role of surgery has been questioned. These alternative approaches are set against a changing epidemiological background whereby adenocarcinoma has become the predominant tumor type, at least in the western world. In recent times an emphasis has been placed on the better selection of patients, predominantly based on data that shows a markedly improved survival in those who exhibit a response to neo-adjuvant therapy. In this article we review the major studies and discuss new approaches to the management of patients with locally advanced cancer of the esophagus

Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards

Myeloid-derived suppressor cells (MDSCs) have emerged as major regulators of immune responses in cancer and other pathological conditions. In recent years, ample evidence supports key contributions of MDSC to tumour progression through both immune-mediated mechanisms and those not directly associated with immune suppression. MDSC are the subject of intensive research with >500 papers published in 2015 alone. However, the phenotypic, morphological and functional heterogeneity of these cells generates confusion in investigation and analysis of their roles in inflammatory responses. The purpose of this communication is to suggest characterization standards in the burgeoning field of MDSC research

Combination of Conservative and Interventional Therapy Strategies for Intra- and Extrahepatic Cholangiocellular Carcinoma: A Retrospective Survival Analysis

Background. Due to the predominantly advanced stage at the time of diagnosis treatment of cholangiocarcinoma is difficult. Apart from surgical resection, interventional treatment strategies are increasingly used in advanced stage tumours. The aim of the study was a retrospective comparison of the effect of the various forms of treatment on morbidity and mortality. Method. A total of 195 patients, received either chemotherapy or a combination of photodynamic therapy (PDT) or transarterial chemoembolization (TACE) and chemotherapy. Results. The median survival rate for all patients was 15.6 months, 50.8% were still alive 1 year after diagnosis. Patients, who had previously undergone surgery, survived 17.1 months longer than those without surgical treatment (P < .01). Chemotherapy prolonged the survival by 9.2 months (P = .47). Palliative patients under combination of chemotherapy and PDT survived on average 1.8 months longer (P = .28), with chemotherapy and TACE 9.8 months longer (P = .04) compared to chemotherapy alone. Conclusions. It appears that surgical treatment and chemotherapy combined with PDT or TACE may prolong survival

Constitutive intestinal NF-κB does not trigger destructive inflammation unless accompanied by MAPK activation

Constitutive NF-κB activation in IECs induces inflammatory cytokines and chemokines in the lamina propria, but does not result in overt tissue damage unless acute inflammatory insults are present, causing TNF-dependent destruction and barrier disruption

Molecular therapy for the treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Conventional cytotoxic chemotherapy has failed to show a substantial benefit for patients with HCC. Recently, a number of new drugs targeting molecular mechanisms involved in liver cell transformation have entered into clinical trials and led to encouraging results. In this review we summarise this data and point to a number of new compounds, which are currently being tested and can potentially broaden our therapeutic arsenal even further