Kinskey Jacob C, Tu Yaping N, Tong Wei Lue, Yavorski John M, Blanck George
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, USA.
Cancer Microenviron. 2018 Jun;11(1):51-59. doi: 10.1007/s12307-018-0205-5. Epub 2018 Feb 5.
We assessed pancreatic cancer, lymphocyte infiltrates with a computational genomics approach. We took advantage of tumor-specimen exome files available from the cancer genome atlas to mine T- and B-cell immune receptor recombinations, using highly efficient, scripted algorithms established in several previous reports. Surprisingly, the results indicated that pancreatic cancer exomes represent one of the highest level yields for immune receptor recombinations, significantly higher than two comparison cancers used in this study, head and neck and bladder cancer. In particular, pancreatic cancer exomes have very large numbers of immunoglobulin light chain recombinations, both with regard to number of samples characterized by recovery of such recombinations and with regard to numbers of recombination reads per sample. These results were consistent with B-cell biomarkers, which emphasized the Th2 nature of the pancreatic lymphocyte infiltrate. The tumor specimen exomes with B-cell immune receptor recombination reads represented a dramatically poor outcome, a result not detected with either the head and neck or bladder cancer datasets. The results presented here support the potential value of immunotherapies designed to engineer a Th2 to Th1 shift in treating certain forms of pancreatic cancer.
我们采用计算基因组学方法评估胰腺癌中的淋巴细胞浸润情况。我们利用癌症基因组图谱中可获取的肿瘤样本外显子文件,运用此前多篇报道中建立的高效脚本算法,挖掘T细胞和B细胞免疫受体重组情况。令人惊讶的是,结果表明胰腺癌外显子在免疫受体重组方面的产出水平极高,显著高于本研究中用作对照的另外两种癌症——头颈癌和膀胱癌。特别是,胰腺癌外显子在免疫球蛋白轻链重组方面数量众多,无论是具有此类重组检出的样本数量,还是每个样本的重组读数数量。这些结果与B细胞生物标志物一致,强调了胰腺淋巴细胞浸润的Th2性质。带有B细胞免疫受体重组读数的肿瘤样本外显子预示着极差的预后,这一结果在头颈癌或膀胱癌数据集中均未检测到。此处呈现的结果支持了旨在促使Th2向Th1转变的免疫疗法在治疗某些类型胰腺癌方面的潜在价值。