Abstract 4830: Precision cut cancer tissues slices as human model for the testing of immuno-modulatory compounds
Authors: Bernoth Kristina , Unger Florian T. , Petersen Moiken , Piller Mirja , Krüger Jana , Grabinski Nicole , Juhl Hartmut , David Kerstin A. 
Published: July 2017

Abstract
The goal of personalized medicine is to stratify individual patients to the appropriate treatment. This approach depends on extensive characterization of individual tumors and their sensitivity to therapeutics. In the context of the immunotherapy of cancer, information on the localization, abundance and activation of immune cells within individual tumors gained in importance. In this study, we showed that viable tumors from colorectal cancer patients used within our drug testing platform, exhibit different populations of infiltrating immune cells. Analysis of immune cells was conducted on disaggregated, cells from viable tumor slices. Disaggregation of precision cut cancer tissue slices was performed using the GentleMACS from Miltenyi. Immune cell subsets were analyzed by flow cytometric multiplexing of CD3, CD4, CD8 and CD45. Furthermore, we identified PD1 positive cells among the CD45+/CD3+ lymphocyte population, indicating relevance for anti-PD1 targeted therapy in colorectal cancer. As a proof of principle, precision cut cancer tissue slices were incubated for 24 hours with different concentrations of Nivolumab (anti-PD1). The read out of treatment effects was conducted in regard to cytokine secretions upon compound treatment as well as immune cell composition. Cytokines were analyzed in supernatants of tissue cultures using the proinflammatory panel from Mesoscale Discovery. The results demonstrated that immune cell compositions were stable and uniform within our precision cut cancer tissue slices both pre- and post-cultivation, and pre- and post-treatment with Nivolumab. In contrast, cytokine secretion had changed after treatment. This has been observed for different cytokines, such as INF gamma, IL-2, IL-10 and TNF alpha. A correlation to PD-1 expression on T-cells in different patients has not been seen. In order to optimize preclinical testing of immune-modulatory compounds, preclinical models, which reflect the individual tumor, as well as the individual immune components of the tumor, are mandatory. We have shown here that effects of treatments with an immune-modulatory compound (Nivolumab) were detectable in this system. Therefore, this drug testing platform represents a unique opportunity to test immune-modulatory compounds in a fully human, patient derived model that is close to in vivo situation. In the future, other immune-modulatory classes of compounds have to be tested within the system to more comprehensively elucidate the possibilities and limits of this drug testing platform in regard to immunotherapy.
Citation Format: Kristina Bernoth, Florian T. Unger, Moiken Petersen, Mirja Piller, Jana Krüger, Nicole Grabinski, Hartmut Juhl, Kerstin A. David. Precision cut cancer tissues slices as human model for the testing of immuno-modulatory compounds [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4830. doi:10.1158/1538-7445.AM2017-4830