Data from In Silico Modeling of Immunotherapy and Stroma-Targeting Therapies in Human Colorectal Cancer

作者：Jakob Nikolas Kather, Jan Poleszczuk, Meggy Suarez‐Carmona, Johannes Krisam, Pornpimol Charoentong, Nektarios A. Valous, Cleo‐Aron Weis, Luca Tavernar, Florian Leiss, Esther Herpel, Fee Klupp, Alexis Ulrich, Martin Schneider, Alexander Marx, Dirk Jäger, Niels Halama · 年份：2023 · DOI：10.1158/0008-5472.c.6509384 · 研究领域：Cancer Immunotherapy and Biomarkers、Mathematical Biology Tumor Growth、Immune cells in cancer

<div>Abstract<p>Despite the fact that the local immunological microenvironment shapes the prognosis of colorectal cancer, immunotherapy has shown no benefit for the vast majority of colorectal cancer patients. A better understanding of the complex immunological interplay within the microenvironment is required. In this study, we utilized wet lab migration experiments and quantitative histological data of human colorectal cancer tissue samples (<i>n</i> = 20) including tumor cells, lymphocytes, stroma, and necrosis to generate a multiagent spatial model. The resulting data accurately reflected a wide range of situations of successful and failed immune surveillance. Validation of simulated tissue outcomes on an independent set of human colorectal cancer specimens (<i>n</i> = 37) revealed the model recapitulated the spatial layout typically found in human tumors. Stroma slowed down tumor growth in a lymphocyte-deprived environment but promoted immune escape in a lymphocyte-enriched environment. A subgroup of tumors with less stroma and high numbers of immune cells showed high rates of tumor control. These findings were validated using data from colorectal cancer patients (<i>n</i> = 261). Low-density stroma and high lymphocyte levels showed increased overall survival (hazard ratio 0.322, <i>P</i> = 0.0219) as compared with high stroma and high lymphocyte levels. To guide immunotherapy in colorectal cancer, simulation of...