ABSTRACT
Immunotherapy aims to amplify the anticancer immune response through reactivation of the lymphocytic response raised against several tumor neo-antigens. To obtain an effective immune response, this therapeutic approach requires that a number of immunological checkpoints be passed, such as the activation of excitatory costimulatory signals or the avoidance of coinhibitory molecules. Among the immune checkpoints, the interaction of the membrane-bound ligand PD-1 and its receptor PD-L1 has received much attention because of remarkable efficacy in numerous clinical trials for various cancer types, including non-small cell lung cancer (NSCLC). However, several limitations exist with these therapeutic agents when used as monotherapy, with objective responses observed in only 30-40% of patients, with the majority of patients demonstrating innate resistance, and approximately 25% of responders later demonstrating disease progression. Recent developments in the understanding of cancer immunology have the potential to identify mechanisms of innate and acquired resistance to immune checkpoint inhibitors through translational research in human samples. This review focuses on the biological basic principles for immunological checkpoint blockade, and highlights the current status and the perspectives of this therapeutic approach in NSCLC patients.
Subject(s)
Antibodies, Monoclonal/therapeutic use , B7-H1 Antigen/antagonists & inhibitors , Carcinoma, Non-Small-Cell Lung/drug therapy , Immunotherapy , Lung Neoplasms/drug therapy , B7-H1 Antigen/immunology , Carcinoma, Non-Small-Cell Lung/immunology , Humans , Lung Neoplasms/immunology , PrognosisABSTRACT
BACKGROUND: Limited data exist so far on cardiovascular disease biomarkers in patients maintained on a protein-restricted diet for inborn errors of protein metabolism. The present study aimed to analyse plasma cholesterol, lipoproteins, triglycerides and total homocysteine in patients with various inborn errors of protein metabolism in comparison with healthy controls. METHODS: A cross-sectional study of cardiovascular disease biomarkers was conducted in a cohort of patients with inborn errors of protein metabolism: nine phenylketonuria, nine urea cycle defect, six branched chain organic acidaemia and two tyrosinaemia type I patients compared to 30 healthy controls. All patients were on a strict natural protein diet for a mean (SD) period of 5.37 (2.30) years (range 2-9 years). Dietary assessment, plasma cholesterol, triglycerides, lipoproteins and total homocysteine levels were obtained. RESULTS: There were no significant differences in blood lipid studies and total homocysteine levels between patients and controls. CONCLUSIONS: The results obtained in this pilot study suggest that cardiovascular disease biomarkers are not increased in patients with inborn errors of protein metabolism. This may be explained by the possible protective effect of a mono- and polyunsaturated fat rich Mediterranean diet. Additional studies with a larger number of patients are needed to confirm this finding.
Subject(s)
Biomarkers/blood , Cardiovascular Diseases/blood , Metabolism, Inborn Errors/blood , Adolescent , Child , Child, Preschool , Cholesterol/blood , Cross-Sectional Studies , Dietary Proteins/administration & dosage , Female , Homocysteine/blood , Humans , Infant , Lipoproteins/blood , Male , Metabolism, Inborn Errors/complications , Metabolism, Inborn Errors/diet therapy , Nutrition Assessment , Pilot Projects , Risk Factors , Triglycerides/bloodABSTRACT
We report zinc and biotin deficiencies after pancreaticoduodenectomy in a 16 year old female presenting clinically with marked alopecia, total body hair loss, dry skin with scales, and maculopathy with significant vision loss. These micronutrient deficiencies likely occurred due to resection of the duodenum and proximal jejunum, sites of primary absorption of several micronutrients and their protein carriers, including zinc and biotin. Early diagnosis is essential to prevent irreversible sequelae. Adequate supplementation of zinc and biotin as well as dietary advice is needed for clinical improvement.
Subject(s)
Acrodermatitis/etiology , Biotin/deficiency , Pancreaticoduodenectomy/adverse effects , Adolescent , Fatty Liver/etiology , Female , Humans , Malabsorption Syndromes/etiology , Pancreatic Neoplasms/surgery , Zinc/deficiencyABSTRACT
We herein describe a 16-year-old child with acute lymphoblastic leukemia and acute pancreatitis who developed Wernicke's encephalopathy secondary to prolonged total parenteral nutrition (TPN) that lacked vitamin B1 supplementation. The patient showed a direct and complete response to thiamine therapy. Diagnostic challenges are discussed and recommendations for prophylactic vitamin B1 supplementation in children with leukemia who are placed on TPN are made.
