The Efficacy of Tumor Mutation Burden as a Biomarker of Response to Immune Checkpoint Inhibitors.

Cancer is one of the leading causes of death in the world; therefore, extensive research has been dedicated to exploring potential therapeutics, including immune checkpoint inhibitors (ICIs). Initially, programmed-death ligand-1 was the biomarker utilized to predict the efficacy of ICIs. However, its heterogeneous expression in the tumor microenvironment, which is critical to cancer progression, promoted the exploration of the tumor mutation burden (TMB). Research in various cancers, such as melanoma and lung cancer, has shown an association between high TMB and response to ICIs, increasing its predictive value. However, the TMB has failed to predict ICI response in numerous other cancers. Therefore, future research is needed to analyze the variations between cancer types and establish TMB cutoffs in order to create a more standardized methodology for using the TMB clinically. In this review, we aim to explore current research on the efficacy of the TMB as a biomarker, discuss current approaches to overcoming immunoresistance to ICIs, and highlight new trends in the field such as liquid biopsies, next generation sequencing, chimeric antigen receptor T-cell therapy, and personalized tumor vaccines.

Diagnosis of Sesame Allergy: Analysis of Current Practice and Exploration of Sesame Component Ses i 1.

BACKGROUND: Sesame is an allergen of increasing importance. OBJECTIVE: We sought to characterize the outcomes of oral food challenges (OFCs) to sesame and evaluate the diagnostic accuracy of skin prick testing (SPT), sesame, and Ses i 1-specific IgE (sIgE). METHODS: We reviewed sesame OFCs performed at the Mount Sinai pediatric allergy clinic between January 2010 and April 2018. We assessed the accuracy of diagnostic tests by calculating the area under the curve (AUC) of the receiver operating characteristic curves. The association between OFC outcome and sesame sensitization was analyzed using a logistic regression, which was then used to estimate the 95% positive predictive value (PPV) of these tests. RESULTS: We identified 341 patients (69% male, mean age 7.7 years) who underwent sesame OFC. Among 106 (31%) positive OFCs, the median cumulative eliciting dose was 500 mg sesame protein (1/2 teaspoon tahini). Sesame SPT wheal ≥6 mm had sensitivity 54.1% and specificity 87.8%; AUC 0.756 (95% confidence interval [CI], 0.699-0.814). SPT wheal size ≥14 mm had 95% PPV. Sesame-sIgE level did not correlate with OFC outcome. Ses i-sIgE levels were analyzed in 30 patients using the Immuno Solid-phase Allergen Chip (ISAC) microarray and were significantly associated with OFC outcome (AUC: 0.715 [95% CI, 0.541-0.890]). Ses i 1-sIgE ≥0.3 ISAC Standardized Units had sensitivity 58.3% and specificity 83.3%. CONCLUSIONS: This is the largest study of sesame allergy to date. Sesame SPT is a more accurate predictor of sesame allergy compared with sesame sIgE. Ses i 1-sIgE appears promising but requires further study regarding diagnostic accuracy.