Interferon‐γ differentially regulates susceptibility of lung cancer cells to telomerase‐specific cytotoxic T lymphocytes
Interferon‐γ differentially regulates susceptibility of lung cancer cells to telomerase‐specific cytotoxic T lymphocytes
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干扰素-γ差异调节肺癌细胞对端粒酶特异性细胞毒性T淋巴细胞的敏感性
DOI：
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
K. Kuzushima
中科院分区：
文献类型：
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作者：
K. Tajima;Yoshinori Ito;A. Demachi;K. Nishida;Y. Akatsuka;K. Tsujimura;T. Hida;Y. Morishima;H. Kuwano;T. Mitsudomi;Toshitada Takahashi;K. Kuzushima
越来越多的证据表明，来源于人端粒酶逆转录酶催化亚基（hTERT）的肽被CD 8+细胞毒性T淋巴细胞特异性识别。我们研究了人类白细胞抗原（HLA）-A*2402限制性hTERT衍生肽461-469（hTERT 461）特异性CD 8 + T细胞克隆（命名为K3 - 1）的细胞毒性，该克隆通过重复肽刺激从健康供体中建立。该克隆对6个端粒酶活性阳性的HLA-A24阳性肺癌细胞系中的4个表现出细胞毒性，但对4个HLA-A24阴性的例子没有。当用100 U/ml干扰素（IFN）-γ预处理靶细胞48 h时，PC 9细胞对K3 - 1的敏感性增加，但LU 99细胞对K3 - 1的敏感性意外降低。然而，在两种细胞系中，与表位呈递相关的分子（如HLA-A24、与抗原加工相关的转运蛋白、低分子量多肽7和蛋白酶体激活剂28）的表达在IFN-γ处理后类似地增加。使用酸提取肽的CTL测定结果表明，IFN-γ处理后，PC 9细胞上的表位增加，但LU 99细胞上的表位没有增加。半定量逆转录聚合酶链反应显示，LU 99细胞中hTERT的表达减弱，但PC 9细胞中未减弱，这是K3 - 1介导的细胞毒性降低的原因。在从肺癌患者的肺液获得的原代腺癌细胞中也观察到IFN-γ处理后hTERT表达和K3 - 1介导的细胞溶解的减弱。我们的数据强调了肽hTERT 461在肺癌免疫治疗中的实用性，与早期报道的其他恶性肿瘤一样，并表明在治疗方法中需要考虑IFN-γ对hTERT表达的调节。© 2004 Wiley利斯公司
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)‐γ 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‐γ treatment. Results of CTL assays using acid‐extracted peptides indicated that the epitope increased on PC9 cells but not on LU99 cells after IFN‐γ 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‐γ 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‐γ needs to be taken into account in therapeutic approach. © 2004 Wiley‐Liss, Inc.
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DOI：
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发表时间：
1994-08
期刊：
The Journal of biological chemistry
影响因子：
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作者：
C. Realini;W. Dubiel;G. Pratt;K. Ferrell;M. Rechsteiner
通讯作者：
C. Realini;W. Dubiel;G. Pratt;K. Ferrell;M. Rechsteiner
影响因子：
32.4
作者：
Vonderheide, RH;Hahn, WC;Nadler, LM
通讯作者：
Nadler, LM
DOI：
--
发表时间：
2001
期刊：
--
影响因子：
--
作者：
K. Kuzushima;Naomi Hayashi;H. Kimura;T. Tsurumi
通讯作者：
K. Kuzushima;Naomi Hayashi;H. Kimura;T. Tsurumi
影响因子：
56.9
作者：
KIM, NW;PIATYSZEK, MA;SHAY, JW
通讯作者：
SHAY, JW
影响因子：
15.9
作者：
Schultze, JL;Michalak, S;Nadler, LM
通讯作者：
Nadler, LM