Quantitative T-cell repertoire analysis of peripheral blood mononuclear cells from lung cancer patients following long-term cancer peptide vaccination
Quantitative T-cell repertoire analysis of peripheral blood mononuclear cells from lung cancer patients following long-term cancer peptide vaccination
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长期癌症肽疫苗接种后肺癌患者外周血单个核细胞的定量 T 细胞库分析
DOI：
10.1007/s00262-018-2152-x
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Suzuki Hiroyuki
中科院分区：
文献类型：
--
作者：
Takeda Kazuyoshi;Kitaura Kazutaka;Suzuki Ryuji;Owada Yuki;Muto Satoshi;Okabe Naoyuki;Hasegawa Takeo;Osugi Jun;Hoshino Mika;Tsunoda Takuya;Okumura Ko;Suzuki Hiroyuki
治疗性癌症肽疫苗是一种免疫疗法，旨在引起患者的细胞毒性t淋巴细胞（CTL）反应。已经进行了许多治疗性疫苗接种试验，然而，只有少数报告分析了肿瘤抗原特异性ctl上表达的t细胞受体（TCRs）。在这里，我们使用下一代测序（NGS）分析了疫苗诱导的CTL克隆的TCR和两名肺癌患者在长期疫苗治疗过程中外周血单个核细胞（PBMCs）中散装T细胞的TCR库。在这两例患者中，接种来自癌症/睾丸抗原的两种表位肽（上调的肺癌10 （URLC10）和细胞分裂相关1 (CDCA1)）诱导表达各种tcr的特异性ctl。当与urlc10脉冲肿瘤细胞共培养时，所有urlc10特异性CTL克隆均显示Ca2+内流，IFN-γ产生和细胞毒性。此外，在未被URLC10/ mhc多聚体染色的CTL克隆中，CD3 ζ链未被磷酸化。大量PBMCs的TCR库的NGS表明，疫苗肽特异性CTL克隆的频率接近最低可检测阈值水平。这些结果表明，在癌症患者中，疫苗接种诱导抗原特异性CTL在不同时间点表达不同的tcr，并且在长期治疗期间，pbmc中一些CTL克隆得以维持，包括一些不结合肽/ mhc多聚体的tcr。
Therapeutic cancer peptide vaccination is an immunotherapy designed to elicit cytotoxic T-lymphocyte (CTL) responses in patients. A number of therapeutic vaccination trials have been performed, nevertheless there are only a few reports that have analyzed the T-cell receptors (TCRs) expressed on tumor antigen-specific CTLs. Here, we use next-generation sequencing (NGS) to analyze TCRs of vaccine-induced CTL clones and the TCR repertoire of bulk T cells in peripheral blood mononuclear cells (PBMCs) from two lung cancer patients over the course of long-term vaccine therapy. In both patients, vaccination with two epitope peptides derived from cancer/testis antigens (upregulated lung cancer 10 (URLC10) and cell division associated 1 (CDCA1)) induced specific CTLs expressing various TCRs. All URLC10-specific CTL clones tested showed Ca2+influx, IFN-γ production, and cytotoxicity when co-cultured with URLC10-pulsed tumor cells. Moreover, in CTL clones that were not stained with the URLC10/MHC-multimer, the CD3 ζ chain was not phosphorylated. NGS of the TCR repertoire of bulk PBMCs demonstrated that the frequency of vaccine peptide-specific CTL clones was near the minimum detectable threshold level. These results demonstrate that vaccination induces antigen-specific CTLs expressing various TCRs at different time points in cancer patients, and that some CTL clones are maintained in PBMCs during long-term treatment, including some with TCRs that do not bind peptide/MHC-multimer.
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一种新的高通量测序方法，用于确定T细胞受体（TCR）α和β曲目的多样性和相似性，并确定潜在的新不变TCRα链。
影响因子：
3
作者：
Kitaura K;Shini T;Matsutani T;Suzuki R
通讯作者：
Suzuki R
从单个T细胞获得的抗原特异性T细胞受体的快速高效克隆和功能评估系统
DOI：
--
发表时间：
2010
期刊：
影响因子：
--
作者：
M.Horii;et.al
通讯作者：
et.al
影响因子：
50.3
作者：
Engels B;Engelhard VH;Sidney J;Sette A;Binder DC;Liu RB;Kranz DM;Meredith SC;Rowley DA;Schreiber H
通讯作者：
Schreiber H
影响因子：
5.2
作者：
Park JH;Jang M;Tarhan YE;Katagiri T;Sasa M;Miyoshi Y;Kalari KR;Suman VJ;Weinshilboum R;Wang L;Boughey JC;Goetz MP;Nakamura Y
通讯作者：
Nakamura Y
影响因子：
64.8
作者：
Gubin, Matthew M.;Zhang, Xiuli;Schuster, Heiko;Caron, Etienne;Ward, Jeffrey P.;Noguchi, Takuro;Ivanova, Yulia;Hundal, Jasreet;Arthur, Cora D.;Krebber, Willem-Jan;Mulder, Gwenn E.;Toebes, Mireille;Vesely, Matthew D.;Lam, Samuel S. K.;Korman, Alan J.;Allison, James P.;Freeman, Gordon J.;Sharpe, Arlene H.;Pearce, Erika L.;Schumacher, Ton N.;Aebersold, Ruedi;Rammensee, Hans-Georg;Melief, Cornelis J. M.;Mardis, Elaine R.;Gillanders, William E.;Artyomov, Maxim N.;Schreiber, Robert D.
通讯作者：
Schreiber, Robert D.