Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington.
Published: May 2020
AI Article Synopsis
Article Abstract
Merkel cell carcinoma (MCC) is often caused by persistent expression of Merkel cell polyomavirus (MCPyV) T-antigen (T-Ag). These non-self proteins comprise about 400 amino acids (AA). Clinical responses to immune checkpoint inhibitors, seen in about half of patients, may relate to T-Ag-specific T cells. Strategies to increase CD8 T-cell number, breadth, or function could augment checkpoint inhibition, but vaccines to augment immunity must avoid delivery of oncogenic T-antigen domains. We probed MCC tumor-infiltrating lymphocytes (TIL) with an artificial antigen-presenting cell (aAPC) system and confirmed T-Ag recognition with synthetic peptides, HLA-peptide tetramers, and dendritic cells (DC). TILs from 9 of 12 (75%) subjects contained CD8 T cells recognizing 1-8 MCPyV epitopes per person. Analysis of 16 MCPyV CD8 TIL epitopes and prior TIL data indicated that 97% of patients with MCPyV MCC had HLA alleles with the genetic potential that restrict CD8 T-cell responses to MCPyV T-Ag. The LT AA 70-110 region was epitope rich, whereas the oncogenic domains of T-Ag were not commonly recognized. Specific recognition of T-Ag-expressing DCs was documented. Recovery of MCPyV oncoprotein-specific CD8 TILs from most tumors indicated that antigen indifference was unlikely to be a major cause of checkpoint inhibition failure. The myriad of epitopes restricted by diverse HLA alleles indicates that vaccination can be a rational component of immunotherapy if tumor immune suppression can be overcome, and the oncogenic regions of T-Ag can be modified without impacting immunogenicity.
About the authors: Yakup Ülger, MD, is Associate Professor Dr., Department of Gastroenterology, Faculty of Medicine, Çukurova University, Adana, Turkey.
Background: Merkel cell carcinoma (MCC) is a rare but highly aggressive cutaneous malignancy. Immune checkpoint inhibition (ICI) with PD-(L)1 blockade has significantly improved treatment outcomes in metastatic disease. In patients with primary resistance to PD-(L)1 inhibition, a high overall response rate (ORR) of 50% to later-line ipilimumab plus nivolumab (IPI/NIVO) has been demonstrated.
Objectives: Oral cancer (OC) is the most common malignant tumor of the head and neck (HN) and ranks 16th among the most frequently diagnosed cancers worldwide. A systematic review and meta-analysis aimed to provide an evidence-based analysis of the relationship between polyomaviruses and oral cancer.
Methods: The global online databases was used to identify relevant studies published between January 2000 and September 2024.
Polymeric carriers have long been recognized as some of the most effective and promising systems for nucleic acid delivery. In this study, we utilized an anionic di-block co-polymer, PEG-PLE, to enhance the performance of lipid-modified PEI (C14-PEI) nanoplexes for delivering Cas9 mRNA and sgRNA targeting KRAS G12S mutations in lung cancer cells. Our results demonstrated that PEG-PLE, when combined with C14-PEI at a weight-to-weight ratio of 0.
