PMID- 37415627
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230718
IS  - 1792-1082 (Electronic)
IS  - 1792-1074 (Print)
IS  - 1792-1074 (Linking)
VI  - 26
IP  - 2
DP  - 2023 Aug
TI  - Generation of novel complete HLA class I monoallelic cell lines used in an MHC 
      stabilization assay for neoantigen evaluation.
PG  - 324
LID - 10.3892/ol.2023.13910 [doi]
LID - 324
AB  - Immunogenic neoantigens derived from somatic mutations in cancer have been 
      identified through clinical studies with the cloning of tumor-infiltrating T 
      cells, and cancer driver gene mutation-derived epitopes have been reported; 
      however, these are rare. At present, the validation of epitopes predicted in 
      silico is difficult as human T-cell clonal diversity cannot be reproduced in 
      vitro or in experimental animal models. To confirm the epitope peptides presented 
      by human leukocyte antigen (HLA) class I molecules predicted in silico, 
      biochemical methods such as major histocompatibility complex (MHC) stabilization 
      assays and mass spectrometry-mediated identification have been developed based on 
      HLA-A*02:01 monoallelic T2 cells and HLA-C*01:02 monoallelic LCL721.221 cells. 
      Therefore, in the present study, to prevent confusion due to peptide 
      cross-presentation among HLA molecules, HLA class I monoallelic B-cell clones 
      were generated from the TISI cell line by knocking out HLA-ABC and TAP2, and 
      knocking in HLA alleles. To explore cancer driver mutations as potential targets 
      for immunotherapy, exome sequencing data from 5,143 patients with cancer enrolled 
      in a comprehensive genome analysis project at the Shizuoka Cancer Center were 
      used to identify somatic amino acid substituted mutations and the 50 most 
      frequent mutations in five genes, TP53, EGFR, PIK3CA, KRAS and BRAF, were 
      identified. Using NetMHC4.1, the present study predicted whether epitopes derived 
      from these mutations are presented on major HLA-ABC alleles in Japanese 
      individuals and synthesized 138 peptides for MHC stabilization assays. The 
      authors also attempted to examine the candidate epitopes at physiological 
      temperatures by using antibody clone G46-2.6, which can detect HLA-ABC, 
      independent of beta2-microglobulin association. In the assays, although the 
      peptide-induced HLA expression levels were associated with the predicted 
      affinities, the respective HLA alleles exhibited varying degrees of 
      responsiveness, and unexpectedly, p53-mutant epitopes with predicted weak 
      affinities exhibited strong responses. These results suggested that MHC 
      stabilization assays using completely monoallelic HLA-expressing B-cell lines are 
      useful for evaluating the presentation of neoantigen epitopes.
CI  - Copyright: (c) Iizuka et al.
FAU - Iizuka, Akira
AU  - Iizuka A
AD  - Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka 
      411-8777, Japan.
FAU - Akiyama, Yasuto
AU  - Akiyama Y
AD  - Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka 
      411-8777, Japan.
FAU - Sakura, Naoki
AU  - Sakura N
AD  - Medical Genetics Division, Shizuoka Cancer Center Research Institute, Shizuoka 
      411-8777, Japan.
FAU - Kanematsu, Akari
AU  - Kanematsu A
AD  - Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka 
      411-8777, Japan.
FAU - Kikuchi, Yasufumi
AU  - Kikuchi Y
AD  - Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka 
      411-8777, Japan.
FAU - Nagashima, Takeshi
AU  - Nagashima T
AD  - Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute, 
      Shizuoka 411-8777, Japan.
AD  - SRL, Inc., Tokyo 163-0409, Japan.
FAU - Urakami, Kenichi
AU  - Urakami K
AD  - Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute, 
      Shizuoka 411-8777, Japan.
FAU - Shimoda, Yuji
AU  - Shimoda Y
AD  - Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute, 
      Shizuoka 411-8777, Japan.
FAU - Ohshima, Keiichi
AU  - Ohshima K
AD  - Medical Genetics Division, Shizuoka Cancer Center Research Institute, Shizuoka 
      411-8777, Japan.
FAU - Shiomi, Akio
AU  - Shiomi A
AD  - Division of Colon and Rectal Surgery, Shizuoka Cancer Center Hospital, Shizuoka 
      411-8777, Japan.
FAU - Ohde, Yasuhisa
AU  - Ohde Y
AD  - Division of Thoracic Surgery, Shizuoka Cancer Center Hospital, Shizuoka 411-8777, 
      Japan.
FAU - Terashima, Masanori
AU  - Terashima M
AD  - Division of Gastric Surgery, Shizuoka Cancer Center Hospital, Shizuoka 411-8777, 
      Japan.
FAU - Uesaka, Katsuhiko
AU  - Uesaka K
AD  - Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, 
      Shizuoka 411-8777, Japan.
FAU - Mukaigawa, Takashi
AU  - Mukaigawa T
AD  - Division of Head and Neck Surgery, Shizuoka Cancer Center Hospital, Shizuoka 
      411-8777, Japan.
FAU - Hirashima, Yasuyuki
AU  - Hirashima Y
AD  - Division of Gynecology, Shizuoka Cancer Center Hospital, Shizuoka 411-8777, 
      Japan.
FAU - Yoshikawa, Shusuke
AU  - Yoshikawa S
AD  - Division of Dermatology, Shizuoka Cancer Center Hospital, Shizuoka 411-8777, 
      Japan.
FAU - Katagiri, Hirohisa
AU  - Katagiri H
AD  - Division of Orthopedic Oncology, Shizuoka Cancer Center Hospital, Shizuoka 
      411-8777, Japan.
FAU - Sugino, Takashi
AU  - Sugino T
AD  - Division of Pathology, Shizuoka Cancer Center Hospital, Shizuoka 411-8777, Japan.
FAU - Takahashi, Mitsuru
AU  - Takahashi M
AD  - Division of Orthopedic Oncology, Shizuoka Cancer Center Hospital, Shizuoka 
      411-8777, Japan.
FAU - Kenmotsu, Hirotsugu
AU  - Kenmotsu H
AD  - Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, Shizuoka 
      411-8777, Japan.
FAU - Yamaguchi, Ken
AU  - Yamaguchi K
AD  - Office of The President, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
LA  - eng
PT  - Journal Article
DEP - 20230613
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC10320429
OTO - NOTNLM
OT  - CRISPR
OT  - HLA
OT  - MHC
OT  - antigen peptide transporter 2
OT  - driver
OT  - immunotherapy
OT  - neoantigen
COIS- The authors declare that they have no competing interests.
EDAT- 2023/07/07 06:42
MHDA- 2023/07/07 06:43
PMCR- 2023/06/13
CRDT- 2023/07/07 03:54
PHST- 2023/01/17 00:00 [received]
PHST- 2023/05/16 00:00 [accepted]
PHST- 2023/07/07 06:43 [medline]
PHST- 2023/07/07 06:42 [pubmed]
PHST- 2023/07/07 03:54 [entrez]
PHST- 2023/06/13 00:00 [pmc-release]
AID - OL-26-2-13910 [pii]
AID - 10.3892/ol.2023.13910 [doi]
PST - epublish
SO  - Oncol Lett. 2023 Jun 13;26(2):324. doi: 10.3892/ol.2023.13910. eCollection 2023 
      Aug.