Tabitha R Hudock, Vayda R Barker, Brandon J Manley, Andrea Chobrutskiy, Boris I Chobrutskiy, Michael J Diaz, Joanna J Song, George Blanck
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引用次数: 0
Abstract
Background: Immunogenomics approaches to the characterization of renal cell carcinoma (RCC) have helped to better our understanding of the features of RCC immune dysfunction. However, much is still unknown with regard to specific immune interactions and their impact in the tumor microenvironment.
Objective: This study applied chemical complementarity scoring for the TRB complementarity determining region-3 (CDR3) amino acid sequences and cancer testis antigens (CTAs) to determine whether such complementarity correlated with survival and the expression of immune marker genes.
Methods: TRB recombination reads from RCC tumor samples from RNAseq files obtained from two separate databases, Moffitt Cancer Center and The Cancer Genome Atlas (TCGA), were evaluated. Chemical complementarity scores (CSs) were calculated for TRB CDR3-CTA pairs and survival assessments based on those CSs were performed.
Results: Moffitt Cancer Center and TCGA cases representing the upper 50th percentile of chemical CSs for TRB CDR3 amino acid sequences and the CTA POTEA were found to be associated with a better overall survival (OS) Also, greater tumor RNA expression of multiple immune signature genes, including granzyme A, granzyme B, and interferon-gamma were correlated with the higher chemical CSs.
Conclusions: These results indicate that TRB CDR3-CTA chemical complementarity scoring may be useful in distinguishing RCC cases with a productive, anti-tumor immune response from cases where basic immune parameter assessments are inconsistent with a productive immune response.
背景:免疫基因组学方法表征肾细胞癌(RCC)有助于我们更好地理解肾细胞癌免疫功能障碍的特征。然而，关于特异性免疫相互作用及其在肿瘤微环境中的影响，仍有许多未知。目的:本研究采用化学补补性评分法对TRB补补性测定区3 (CDR3)氨基酸序列和癌睾丸抗原(cta)进行评分，以确定这种补补性是否与生存和免疫标记基因的表达相关。方法:对来自Moffitt Cancer Center和The Cancer Genome Atlas (TCGA)两个独立数据库的RNAseq文件中RCC肿瘤样本的TRB重组reads进行评估。计算TRB CDR3-CTA对的化学互补评分(CSs)，并根据这些评分进行生存评估。结果:Moffitt Cancer Center和TCGA的病例中，TRB CDR3氨基酸序列和CTA POTEA化学CSs的前50百分位被发现与更好的总生存率(OS)相关。此外，多种免疫特征基因(包括颗粒酶a、颗粒酶B和干扰素- γ)的肿瘤RNA表达量较高与较高的化学CSs相关。结论:这些结果表明，TRB CDR3-CTA化学互补评分可能有助于区分具有生产性抗肿瘤免疫应答的RCC病例和基本免疫参数评估与生产性免疫应答不一致的病例。
期刊介绍：
Concentrating on molecular biomarkers in cancer research, Cancer Biomarkers publishes original research findings (and reviews solicited by the editor) on the subject of the identification of markers associated with the disease processes whether or not they are an integral part of the pathological lesion.
The disease markers may include, but are not limited to, genomic, epigenomic, proteomics, cellular and morphologic, and genetic factors predisposing to the disease or indicating the occurrence of the disease. Manuscripts on these factors or biomarkers, either in altered forms, abnormal concentrations or with abnormal tissue distribution leading to disease causation will be accepted.
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