Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Cancer Discov. 2017 Oct;7(10):1088-1097. doi: 10.1158/2159-8290.CD-17-0256. Epub 2017 Jul 21.
Genomic intratumor heterogeneity (ITH) may be associated with postsurgical relapse of localized lung adenocarcinomas. Recently, mutations, through generation of neoantigens, were shown to alter tumor immunogenicity through T-cell responses. Here, we performed sequencing of the T-cell receptor (TCR) in 45 tumor regions from 11 localized lung adenocarcinomas and observed substantial intratumor differences in T-cell density and clonality with the majority of T-cell clones restricted to individual tumor regions. TCR ITH positively correlated with predicted neoantigen ITH, suggesting that spatial differences in the T-cell repertoire may be driven by distinct neoantigens in different tumor regions. Finally, a higher degree of TCR ITH was associated with an increased risk of postsurgical relapse and shorter disease-free survival, suggesting a potential clinical significance of T-cell repertoire heterogeneity. The present study provides insights into the ITH of the T-cell repertoire in localized lung adenocarcinomas and its potential biological and clinical impact. The results suggest that T-cell repertoire ITH may be tightly associated to genomic ITH and disease relapse. .
肿瘤内基因组异质性（ITH）可能与局部肺腺癌手术后的复发有关。最近，通过产生新抗原的突变，被证明可以通过 T 细胞反应改变肿瘤的免疫原性。在这里，我们对 11 例局部肺腺癌的 45 个肿瘤区域进行了 T 细胞受体（TCR）测序，观察到 T 细胞密度和克隆性存在明显的肿瘤内差异，大多数 T 细胞克隆局限于单个肿瘤区域。TCR ITH 与预测的新抗原 ITH 呈正相关，表明 T 细胞库的空间差异可能是由不同肿瘤区域中不同的新抗原驱动的。最后，较高程度的 TCR ITH 与手术后复发风险增加和无病生存期缩短相关，提示 T 细胞库异质性具有潜在的临床意义。本研究提供了对局部肺腺癌中 T 细胞库 ITH 及其潜在生物学和临床影响的深入了解。结果表明，T 细胞库 ITH 可能与基因组 ITH 和疾病复发密切相关。
