Abstract 1099: Organotypic tumor tissue slices provide versatile platform for immuno-oncology

Abstract

Abstract Organotypic tissue slices represent one of the most physiologically-relevant culture systems for studying the tumor microenvironment. The thin slices of tumor cut out using automated vibratome retain the original architecture and cellular composition of the tumor from several days up to weeks depending on the investigated tumor model. The slice culture has been emerging as a versatile platform for studying cancer cell-host cell interactions. However, a thorough characterization of the multicellular organotypic culture system, particularly its immune component, is still unresolved to allow a better understanding of its potential applications. Here, we carried out a comprehensive characterization of immune cell composition in organotypic tumor slices prepared from several different syngeneic mouse tumor models. We generated several syngeneic mouse tumor models and harvested the primary tumors to make tumor slices. We then immunophenotyped the major tumor infiltrating leukocytes (TILs) by flow cytometry to understand the immune makeup of these slices immediately after the harvest, over a period of 7 days and upon treatment of various immuno-modulators. We found that the immune compositions of tumor slices do not deviate from that of the tumor cores, immediately after harvest, across all the syngeneic tumor models. During the 7-day follow-up, despite an initial decline in the overall cell viability which stabilized on day 3, we observed a consistent percentage of TILs out of total viable cells, suggesting that the relative composition of tumor and immune populations can be maintained in the tumor slice over time. Among the TILs, macrophages were the predominant immune cell type detected, similar to that observed in many human solid tumors. Macrophages remained viable till day 7 while other cell types were mostly viable till day 5, providing a window of time sufficient to support many short-term perturbation studies. Further, we found that these immune cell populations were responsive to the treatment with immunomodulators. For example, we observed an upregulation of co-stimulatory markers, CD86 and MHC-II, on macrophages and DCs upon stimulation with the pro-inflammatory cytokine IFN γ, further supporting the application of tumor slice in the study of immuno-oncology. Overall, these data support the approach of utilizing tumor slice culture as a platform for studying tumor microenvironment and evaluating efficacy of immune modulatory drugs. Citation Format: Ramya Sivakumar, Marina Chan, Raymond Yeung, Taranjit S. Gujral. Organotypic tumor tissue slices provide versatile platform for immuno-oncology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1099.