Reiman Derek, Sha Lingdao, Ho Irvin, Tan Timothy, Lau Denise, Khan Aly A
Tempus Labs, Chicago, IL 60654, USA.
Pac Symp Biocomput. 2019;24:284-295.
Patient responses to cancer immunotherapy are shaped by their unique genomic landscape and tumor microenvironment. Clinical advances in immunotherapy are changing the treatment landscape by enhancing a patient's immune response to eliminate cancer cells. While this provides potentially beneficial treatment options for many patients, only a minority of these patients respond to immunotherapy. In this work, we examined RNA-seq data and digital pathology images from individual patient tumors to more accurately characterize the tumor-immune microenvironment. Several studies implicate an inflamed microenvironment and increased percentage of tumor infiltrating immune cells with better response to specific immunotherapies in certain cancer types. We developed NEXT (Neural-based models for integrating gene EXpression and visual Texture features) to more accurately model immune infiltration in solid tumors. To demonstrate the utility of the NEXT framework, we predicted immune infiltrates across four different cancer types and evaluated our predictions against expert pathology review. Our analyses demonstrate that integration of imaging features improves prediction of the immune infiltrate. Of note, this effect was preferentially observed for B cells and CD8 T cells. In sum, our work effectively integrates both RNA-seq and imaging data in a clinical setting and provides a more reliable and accurate prediction of the immune composition in individual patient tumors.
患者对癌症免疫疗法的反应取决于其独特的基因组格局和肿瘤微环境。免疫疗法的临床进展正在通过增强患者的免疫反应以消除癌细胞来改变治疗格局。虽然这为许多患者提供了潜在有益的治疗选择,但只有少数患者对免疫疗法有反应。在这项工作中,我们检查了来自个体患者肿瘤的RNA测序数据和数字病理图像,以更准确地表征肿瘤免疫微环境。几项研究表明,在某些癌症类型中,炎症微环境和肿瘤浸润免疫细胞百分比增加与对特定免疫疗法的更好反应相关。我们开发了NEXT(用于整合基因表达和视觉纹理特征的基于神经的模型),以更准确地模拟实体瘤中的免疫浸润。为了证明NEXT框架的实用性,我们预测了四种不同癌症类型中的免疫浸润,并根据专家病理审查评估了我们 的预测。我们的分析表明,成像特征的整合改善了对免疫浸润的预测。值得注意的是,这种效应在B细胞和CD8 T细胞中尤为明显。总之,我们的工作在临床环境中有效地整合了RNA测序和成像数据,并为个体患者肿瘤中的免疫组成提供了更可靠和准确的预测。