PMID- 15095306
OWN - NLM
STAT- MEDLINE
DCOM- 20040614
LR  - 20171116
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 110
IP  - 3
DP  - 2004 Jun 20
TI  - Interferon-gamma differentially regulates susceptibility of lung cancer cells to 
      telomerase-specific cytotoxic T lymphocytes.
PG  - 403-12
AB  - There is accumulating evidence that peptides derived from the catalytic subunit 
      of human telomerase reverse transcriptase (hTERT) are specifically recognized by 
      CD8+ cytotoxic T lymphocytes. We investigated the cytotoxicity of a human 
      leukocyte antigen (HLA)-A*2402-restricted hTERT-derived peptide 461-469 
      (hTERT461)-specific CD8+ T-cell clone, designated as K3-1, established from a 
      healthy donor by repetitive peptide stimulation. This clone exhibited 
      cytotoxicity against 4 out of 6 HLA-A24-positive lung cancer cell lines with 
      positive telomerase activity but not 4 HLA-A24-negative examples. When the target 
      cells were pretreated with 100 U/ml of interferon (IFN)-gamma for 48 hr, the 
      susceptibility to K3-1 increased with PC9 cells but unexpectedly decreased with 
      LU99 cells. However, in both cell lines, the expression of molecules associated 
      with epitope presentation such as HLA-A24, transporters associated with antigen 
      processing, low molecular weight polypeptide 7 and proteasome activator 28 was 
      similarly increased after IFN-gamma treatment. Results of CTL assays using 
      acid-extracted peptides indicated that the epitope increased on PC9 cells but not 
      on LU99 cells after IFN-gamma treatment. Semi-quantitative reverse transcriptase 
      polymerase chain reaction disclosed that the expression of hTERT was attenuated 
      in LU99 but not in PC9 cells, accounting for the decreased cytotoxicity mediated 
      by K3-1. The attenuation of the hTERT expression and K3-1-mediated cell lysis 
      after IFN-gamma treatment was also observed in primary adenocarcinoma cells 
      obtained from pulmonary fluid of a lung cancer patient. Our data underline the 
      utility of peptide hTERT461 in immunotherapy for lung cancer, as with other 
      malignancies reported earlier, and suggest that modulation of hTERT expression by 
      IFN-gamma needs to be taken into account in therapeutic approach.
CI  - Copyright 2004 Wiley-Liss, Inc.
FAU - Tajima, Kouhei
AU  - Tajima K
AD  - Division of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan.
FAU - Ito, Yoshinori
AU  - Ito Y
FAU - Demachi, Ayako
AU  - Demachi A
FAU - Nishida, Keiko
AU  - Nishida K
FAU - Akatsuka, Yoshiki
AU  - Akatsuka Y
FAU - Tsujimura, Kunio
AU  - Tsujimura K
FAU - Hida, Toyoaki
AU  - Hida T
FAU - Morishima, Yasuo
AU  - Morishima Y
FAU - Kuwano, Hiroyuki
AU  - Kuwano H
FAU - Mitsudomi, Tetsuya
AU  - Mitsudomi T
FAU - Takahashi, Toshitada
AU  - Takahashi T
FAU - Kuzushima, Kiyotaka
AU  - Kuzushima K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (CD40 Antigens)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Epitopes)
RN  - 0 (HLA-A Antigens)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Peptides)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.7.49 (Telomerase)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Blotting, Western
MH  - CD40 Antigens/biosynthesis
MH  - CD8-Positive T-Lymphocytes/metabolism
MH  - Cell Line, Tumor
MH  - Cysteine Endopeptidases/metabolism
MH  - DNA-Binding Proteins
MH  - Dose-Response Relationship, Drug
MH  - Down-Regulation
MH  - Epitopes/chemistry
MH  - Flow Cytometry
MH  - *Gene Expression Regulation, Neoplastic
MH  - HLA-A Antigens/chemistry
MH  - Humans
MH  - Immunotherapy
MH  - Interferon-gamma/metabolism/*physiology
MH  - Leukocytes, Mononuclear/metabolism
MH  - Lung Neoplasms/*metabolism/*therapy
MH  - Multienzyme Complexes/metabolism
MH  - Peptides/chemistry
MH  - Proteasome Endopeptidase Complex
MH  - Retroviridae/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - T-Lymphocytes, Cytotoxic/*metabolism
MH  - Telomerase/*metabolism
EDAT- 2004/04/20 05:00
MHDA- 2004/06/15 05:00
CRDT- 2004/04/20 05:00
PHST- 2004/04/20 05:00 [pubmed]
PHST- 2004/06/15 05:00 [medline]
PHST- 2004/04/20 05:00 [entrez]
AID - 10.1002/ijc.20139 [doi]
PST - ppublish
SO  - Int J Cancer. 2004 Jun 20;110(3):403-12. doi: 10.1002/ijc.20139.