Clonal expansion of antitumor T cells in breast cancer correlates with response to neoadjuvant chemotherapy.
Clonal expansion of antitumor T cells in breast cancer correlates with response to neoadjuvant chemotherapy.
复制标题
DOI：
10.3892/ijo.2016.3540
复制
发表时间：
2016-08
影响因子：
5.2
通讯作者：
Nakamura Y
中科院分区：
文献类型：
--
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
肿瘤的免疫微环境在化疗的治疗反应中起着至关重要的作用。癌症组织由抗肿瘤和促肿瘤免疫细胞和分子之间的复杂网络组成；因此，必须对肿瘤免疫状况进行全面分析，以更好地了解免疫微环境在抗癌治疗反应中的作用。在这项研究中，我们对 19 名乳腺癌患者新辅助化疗 (NAC) 前后的癌组织中的肿瘤浸润 T 细胞 (TIL) 进行了 T 细胞受体 (TCR) 谱分析。 5 例显示 CR（完全缓解），10 例显示 PR（部分缓解），4 例显示 SD/PD（疾病稳定/疾病进展）。根据TCR测序结果，我们计算了TCRβ链的多样性指数，发现在NAC显示CR或PR的患者中可以检测到TIL的克隆扩增。值得注意的是，CR患者的NAC后肿瘤中TCR的多样性进一步降低。我们的定量 RT-PCR 还显示，CR 病例 NAC 后肿瘤中 CD8/Foxp3 的表达比显着升高（p=0.0032），表明这些肿瘤中抗肿瘤 T 细胞被激活并富集。总的来说，我们的研究结果表明，抗肿瘤 T 细胞的克隆扩增可能是与化疗反应相关的关键因素，并且它们的 TCR 序列可能适用于在肿瘤复发时为个体乳腺癌患者开发 TCR 工程 T 细胞治疗。
The immune microenvironment of tumor plays a critical role in therapeutic responses to chemotherapy. Cancer tissues are composed of a complex network between anti-tumor and pro-tumor immune cells and molecules; therefore a comprehensive analysis of the tumor immune condition is imperative for better understanding of the roles of the immune microenvironment in anticancer treatment response. In this study, we performed T cell receptor (TCR) repertoire analysis of tumor infiltrating T cells (TILs) in cancer tissues of pre- and post-neoadjuvant chemotherapy (NAC) from 19 breast cancer patients; five cases showed CR (complete response), ten showed PR (partial response), and four showed SD/PD (stable disease/progressive disease) to the treatment. From the TCR sequencing results, we calculated the diversity index of the TCRβ chain and found that clonal expansion of TILs could be detected in patients who showed CR or PR to NAC. Noteworthy, the diversity of TCR was further reduced in the post-NAC tumors of CR patients. Our quantitative RT-PCR also showed that expression ratio of CD8/Foxp3 was significantly elevated in the post-NAC tumors of CR cases (p=0.0032), indicating that antitumor T cells were activated and enriched in these tumors. Collectively, our findings suggest that the clonal expansion of antitumor T cells may be a critical factor associated with response to chemotherapy and that their TCR sequences might be applicable for the development of TCR-engineered T cells treatment for individual breast cancer patients when their tumors relapse.