Asset Details
Do you wish to reserve the book?
Neoantigen screening identifies broad TP53 mutant immunogenicity in patients with epithelial cancers
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Neoantigen screening identifies broad TP53 mutant immunogenicity in patients with epithelial cancers
Do you wish to request the book?
Neoantigen screening identifies broad TP53 mutant immunogenicity in patients with epithelial cancers
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Neoantigen screening identifies broad TP53 mutant immunogenicity in patients with epithelial cancers
2019
Overview
The TP53 gene, encoding the critical p53 tumor suppressor, is the most commonly mutated gene in cancer. Intratumoral T cell responses to mutations occurring frequently at certain TP53 positions, termed hot spots, have not been systematically studied. The 8 most commonly mutated positions in TP53 were found in 33 (24%) of 140 common epithelial tumors analyzed. A TP53-specific screening assay was developed to evaluate T cell responses to these p53 neoepitopes presented though intracellular (tandem minigene) and extracellular (pulsed peptide) pathways on autologous antigen-presenting cells expressing all human leukocyte antigen (HLA) class I and II molecules. Tumor-infiltrating lymphocytes (TILs) from 11 patients recognized autologous p53 neoantigens, which accounted for 8% and 39% of all patients sequenced (n = 140) and screened (n = 28), respectively. These responses were restricted by a variety of HLA restriction elements, including common class I (A*02:01) and class II (DPB1*02:01 and DRB1*13:01) alleles. T cell receptors (TCRs) were identified from TP53 mutation-reactive helper (CD4) and cytotoxic (CD8) T cells, and TIL and TCR gene-engineered T cells recognized tumor cell lines endogenously expressing HLA and mutant TP53. Thus, the most commonly mutated gene in cancer, TP53, appears to be immunogenic and represents an attractive candidate for evaluating targeted immune cancer therapies.
Publisher
American Society for Clinical Investigation
Subject
/ Animals
/ Antigens
/ Antigens, Neoplasm - genetics
/ Antigens, Neoplasm - immunology
/ Cancer
/ CD4-Positive T-Lymphocytes - immunology
/ CD4-Positive T-Lymphocytes - pathology
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - pathology
/ DNA
/ Female
/ Genes
/ Histocompatibility antigen HLA
/ HLA-DP beta-Chains - genetics
/ HLA-DP beta-Chains - immunology
/ Humans
/ Male
/ Mice
/ Mutation
/ Neoplasms, Glandular and Epithelial - genetics
/ Neoplasms, Glandular and Epithelial - immunology
/ Neoplasms, Glandular and Epithelial - pathology
/ Patients
/ Peptides
/ T cells
/ Tumor Suppressor Protein p53 - genetics
/ Tumor Suppressor Protein p53 - immunology
/ Tumor-infiltrating lymphocytes
/ Tumors
