Tamura Kenji, Hazama Shoichi, Yamaguchi Rui, Imoto Seiya, Takenouchi Hiroko, Inoue Yuka, Kanekiyo Shinsuke, Shindo Yoshitaro, Miyano Satoru, Nakamura Yusuke, Kiyotani Kazuma
Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
Oncol Lett. 2016 Jun;11(6):3643-3649. doi: 10.3892/ol.2016.4465. Epub 2016 Apr 19.
The aim of the present study was to characterize infiltrated T cell clones that define the tumor immune environment and are important in the response to treatment in patients with advanced colorectal cancer (CRC). In order to explore predictive biomarkers for the efficacy of immunochemotherapies, T cell receptor (TCR) repertoire analysis was performed using blood samples and tumor tissues obtained from patients with advanced CRC that had been treated with a combination of five-cancer peptide vaccines and oxaliplatin-based chemotherapy. The TCR-α/β complementary DNAs (cDNAs), prepared from the messenger RNAs (mRNAs) obtained from 17 tumor tissues and 39 peripheral blood mononuclear cells of 9 CRC patients at various time points, were sequenced. The oligoclonal enrichment of certain TCR sequences was identified in tumor tissues and blood samples; however, only a few TCR sequences with a frequency of >0.1% were commonly detected in pre- and post-treatment tumor tissues, or in post-treatment blood and tissue samples. The average correlation coefficients of the TCR-α and TCR-β clonotype frequencies between the post-treatment tumor tissues and blood samples were 0.023 and 0.035, respectively, and were much lower compared with the correlation coefficients of the TCR-α and TCR-β clonotype frequencies between pre- and post-treatment blood samples (0.430 and 0.370, respectively), suggesting that T cell populations in tumor tissues vary from those in blood. Although the sample size was small, a tendency for the TCR diversity in tumor tissues to drastically decrease during the treatment was indicated in two patients, who exhibited a longer progression-free survival time. The results of the present study suggest that TCR diversity scores in tissues may be a useful predictive biomarker for the therapeutic effect of immunochemotherapy for patients with advanced CRC.
本研究的目的是对浸润性T细胞克隆进行表征，这些克隆定义了肿瘤免疫环境，并且在晚期结直肠癌（CRC）患者的治疗反应中起重要作用。为了探索免疫化疗疗效的预测生物标志物，使用从接受五种癌症肽疫苗和奥沙利铂为基础的化疗联合治疗的晚期CRC患者获得的血液样本和肿瘤组织进行了T细胞受体（TCR）谱分析。对从9例CRC患者在不同时间点获得的17个肿瘤组织和39个外周血单个核细胞的信使核糖核酸（mRNA）制备的TCR-α/β互补脱氧核糖核酸（cDNA）进行测序。在肿瘤组织和血液样本中鉴定出某些TCR序列的寡克隆富集；然而，在治疗前和治疗后的肿瘤组织中，或在治疗后的血液和组织样本中，仅共同检测到少数频率>0.1%的TCR序列。治疗后肿瘤组织和血液样本之间TCR-α和TCR-β克隆型频率的平均相关系数分别为0.023和0.035，与治疗前和治疗后血液样本之间TCR-α和TCR-β克隆型频率的相关系数（分别为0.430和0.370）相比要低得多，这表明肿瘤组织中的T细胞群体与血液中的不同。尽管样本量较小，但两名无进展生存期较长的患者显示出肿瘤组织中TCR多样性在治疗期间急剧下降的趋势。本研究结果表明，组织中的TCR多样性评分可能是晚期CRC患者免疫化疗治疗效果的有用预测生物标志物。
