Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, 12901, Bruce B. Downs Bd. MDC7, Tampa, FL, 33612, USA.
Immunology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.
J Neurooncol. 2018 Dec;140(3):697-704. doi: 10.1007/s11060-018-03001-1. Epub 2018 Oct 31.
The immune system plays an important role in cancer survival and disease progression, but the role of the immune system in lower grade glioma (LGG) is largely unknown METHODS: To investigate the relationship between lymphocyte infiltration into the LGG microenvironment and LGG survival, we used a genomics approach to recover productive V(D)J recombination sequences from primary tumor, whole exome sequence files available via the cancer genome atlas RESULTS: Increased T-cell receptor V(D)J read recovery, indicating increased T-lymphocyte infiltration into the primary tumor site, strongly correlated with decreased overall and disease-free survival; and with a more advanced cancer grade. In addition, this result was more significant than related results obtainable using RNASeq-based, T-cell biomarkers, similar to a recently reported case for pancreatic cancer, where the recovery of BCR recombination reads from WXS files clearly associated with reduced survival, despite the fact that no such association was demonstrable with B-cell based, RNASeq biomarkers CONCLUSIONS: Overall, the results presented here support V(D)J recombination read recovery, from whole exome files, as a uniquely useful biomarker for distinct LGG survival rates.
免疫系统在癌症的生存和疾病进展中起着重要作用,但免疫系统在低级别胶质瘤(LGG)中的作用在很大程度上尚不清楚。
为了研究淋巴细胞浸润 LGG 微环境与 LGG 生存之间的关系,我们使用基因组学方法从原发性肿瘤中恢复有功能的 V(D)J 重组序列,这些序列可通过癌症基因组图谱获得全外显子序列文件。
T 细胞受体 V(D)J 阅读恢复增加,表明 T 淋巴细胞浸润原发性肿瘤部位增加,与总生存率和无病生存率降低密切相关;与更高级别的癌症分级相关。此外,与基于 RNASeq 的 T 细胞生物标志物的相关结果相比,这一结果更为显著,类似于最近报道的胰腺癌病例,尽管无法用基于 B 细胞的 RNASeq 生物标志物证明这种关联,但从 WXS 文件中恢复 BCR 重组阅读与降低生存率明显相关。
总体而言,这里提出的结果支持从全外显子文件中恢复 V(D)J 重组阅读,作为一种独特的有用生物标志物,可用于预测不同的 LGG 生存率。