Specific immune cell and lymphatic vessel signatures identified by image analysis in renal cancer

Anti-angiogenic therapy and immune checkpoint inhibition are novel treatment strategies for patients with renal cell carcinoma. Various components and structures of the tumor microenvironment are potential predictive biomarkers and also attractive treatment targets. Macrophages, tumor infiltrating lymphocytes, vascular and lymphatic vessels represent an important part of the tumor immune environment, but their functional phenotypes and relevance for clinical outcome are yet ill defined. We applied Tissue Phenomics methods including image analysis for the standardized quantification of specific components and structures within the tumor microenvironment to profile tissue sections from 56 clear cell renal cell carcinoma patients. A characteristic composition and unique spatial relationship of CD68+ macrophages and tumor infiltrating lymphocytes correlated with overall survival. An inverse relationship was found between vascular (CD34) and lymphatic vessel (LYVE1) density. In addition, outcome was significantly better in patients with high blood vessel density in the tumors, whereas increased lymphatic vessel density in the tumors was associated with worse outcome. The Tissue Phenomics imaging analysis approach allowed visualization and simultaneous quantification of immune environment components, adding novel contextual information, and biological insights with potential applications in treatment response prediction.