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Published on: May 14, 2020
Specific immune cell and lymphatic vessel signatures identified by image analysis in renal cancer
Peter Schraml1, Maria Athelogou2, Thomas Hermanns3
1Department of Pathology and Molecular Pathology, University Hospital Zurich and University Zurich, Schmelzbergstrasse 12, CH-8091, Zurich, Switzerland.
Abstract:
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.
Insights
Tumor microenvironment analysis in renal cell carcinoma reveals macrophage and lymphocyte interactions correlating with survival. Blood vessel density impacts outcomes, offering new insights for predicting treatment response.
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- Novel treatments for renal cell carcinoma (RCC) include anti-angiogenic therapy and immune checkpoint inhibition.
- The tumor microenvironment (TME) contains components like macrophages and lymphocytes, which are potential biomarkers and therapeutic targets.
- The functional roles and clinical relevance of these TME components in RCC are not fully understood.
Purpose of the Study:
- To apply Tissue Phenomics for standardized quantification of TME components in RCC.
- To investigate the correlation between specific TME features and patient outcomes.
- To explore the relationship between vascular and lymphatic vessel density and clinical results.
Main Methods:
- Tissue Phenomics, a quantitative image analysis method, was used to profile tissue sections from 56 clear cell renal cell carcinoma patients.
- Standardized quantification of macrophages (CD68+), tumor-infiltrating lymphocytes, vascular (CD34+), and lymphatic vessels (LYVE1+) within the TME.
- Analysis of spatial relationships between immune cells and vessel densities.
Main Results:
- A specific composition and spatial arrangement of macrophages and tumor-infiltrating lymphocytes were associated with overall survival.
- An inverse relationship was observed between vascular and lymphatic vessel density.
- Higher blood vessel density correlated with better patient outcomes, while increased lymphatic vessel density was linked to worse outcomes.
Conclusions:
- Tissue Phenomics enables comprehensive visualization and quantification of immune and vascular components in the RCC TME.
- These findings provide novel contextual information and biological insights into RCC, potentially aiding in predicting treatment response.
- The study highlights the prognostic significance of TME composition and vascularization in renal cell carcinoma.
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