The Role of Immunotherapy in a Tolerogenic Environment: Current and Future Perspectives for Hepatocellular Carcinoma

In contrast to several tumors whose prognoses are radically affected by novel immunotherapeutic approaches and/or targeted therapies, the outcomes of advanced hepatocellular carcinoma (HCC) remain poor. The underlying cirrhosis that is frequently associated with it complicates medical treatment and often determines survival. The landscape of HCC treatment had included sorafenib as the only drug available for ten years, until 2018, when lenvatinib was approved for treatment. The second-line systemic treatments available for hepatocellular carcinoma include regorafenib, cabozantinib, ramucirumab, and, more recently, immune checkpoint inhibitors. However, the median survival remains below 15 months. The results obtained in clinics should be interpreted whilst considering the peculiar role of the liver as an immune organ. A healthy liver microenvironment ordinarily experiences stimulation by gut-derived antigens. This setup elucidates the response to chronic inflammation and the altered balance between tolerance and immune response in HCC development. This paper provides an overview of the mechanisms involved in HCC pathogenesis, with a special focus on the immune implications, along with current and future clinical perspectives

Ramucirumab in HER-2-positive gastroesophageal adenocarcinoma: An argument for overcoming trastuzumab resistance

Aim: Patients with advanced gastric cancer have a relatively poor prognosis with few therapeutic alternatives beyond first-line therapy. The purpose of this manuscript is to highlight the potential for prolonged responses in patients with HER-2-positive disease. Patients, materials & methods: We analyzed the data of patients diagnosed with HER-2-positive-advanced gastric cancer who progressed on trastuzumab-based combination therapy and subsequently received second-line therapy consisting of ramucirumab in combination with paclitaxel. Results: Most patients had a stable disease after ramucirumab-based therapy (50%, 5/10), median duration to disease control was 8 months. Conclusion: The prolonged duration of response that we observed indicates that an interaction between the EGF pathway and the angiogenesis pathway requires further clinical investigations

Efficacy of a triplet and doublet-based chemotherapy as first-line therapy in patients with HER2-negative metastatic gastric cancer: a retrospective analysis from the clinical practice

The best choice of chemotherapy regimen for patients with metastatic gastric cancer is still debated. Although several studies support a superior efficacy of a triplet chemotherapy regimen over a doublet-based regimen, the magnitude of this benefit appears small and accompanied by an increased toxicity. Based on this background, we evaluated the outcome of patients with HER2-negative metastatic gastric cancer (mGC) who received in the clinical practice a triplet or doublet regimen as first-line therapy. A total of 165 patients (pts) with HER2-negative mGC treated outside of clinical trials at our department with FOLFOX-4 or ECX from 2012 and 2015 were included in our retrospective analysis: FOLFOX-4: 86 pts; ECX: 79 pts. Median progression-free survival (PFS) was 5.1 months for FOLFOX-4 and 5.6 months for ECX regimen, respectively. Median overall survival (OS) was 10.3 months for FOLFOX-4 and 10.9 months for ECX regimens

Zinc supplementation reduces the risk of necrotizing enterocolitis in vert low birth weight neonates: a randomized clinical trial

Objectives & Study: Necrotizing enterocolitis (NEC) remains one of the leading causes of morbidity and mortality in premature neonates1. Modification of immune response and alteration of epithelial barrier play a crucial role in the pathogenesis of NEC. Zinc is an ubiquitous element deeply involved in the development of immune response and essential for epithelial integrity. Preterm neonates are at high risk of zinc deficiency2. In this study we aimed to investigate the efficacy of zinc supplementation in reducing the occurrence of NEC in preterm neonates. Methods: A prospective, double-blind, randomized controlled study was conducted on very low birth weight neonates (birth weight < 1500 g), randomly allocated, at the 7th day of life, in zinc group (receiving 10 mg/d of zinc through a multivitamin product given by oral route) or in placebo group (receiving a similar multivitamin product without zinc). Main endpoint was the rate of neonates presenting NEC. Secondary outcome was mortality rate. Results: We enrolled 97 neonates in the zinc group and 96 in the placebo group. Occurrence of NEC was significantly higher in placebo group (6.3%) compared to the zinc group (0%, p=0.014). Mortality risk was significantly reduced in zinc group (OR 0.275, 95%CI 0.086-0.875, p=0.021). Conclusion: Oral supplementation with high dose of zinc reduces the risk of NEC and mortality in preterm neonates. Additional studies are advocated to investigate the mechanism by which zinc produces observed effects in this particular population