In vitro cancer modeling presents a formidable challenge, as tumor development and progression relies on not only a multiplicity of genetic and molecular alterations, but also physical and spatial factors within a 3-dimensional microenvironment composed of numerous cell types. While recent in vitro models have attempted to integrate tumor architecture by culturing primary human tumors as 3-dimensional spheroids, these models have been composed exclusively of epithelial cells, a reductionist approach that does not recapitulate higher-order phenomena in tumor progression involving stromal and/or immune interactions. We and others have developed a patient derived organoid (PDO) culture system that accurately recapitulates complex tumor architecture and histology including tumor parenchymal, stromal, and immune compartments without the need for grafting in a non-human host. These models represent useful tools for in vitro investigation into the mechanisms governing human tumor immunity, and our current work focuses on the development of PDO models that could potentially be used to predict patient responses to immunotherapy in a clinical setting.

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Publications:

Organoid Modeling of the Tumor Immune Microenvironment. Neal JT, Li X, Zhu J, Giangarra V, Grzeskowiak CL, Ju J, Liu IH, Chiou S, Salhudeen AS, Smith AR, Deutsch BC, Liao L, Zemek AJ, Zhao F, Karlsson K, Schultz LM, Metzner TJ, Nadauld LD, Tseng YY, Alkhairy S, Oh C, Keskula P, Mendoza-Villanueva D, De La Vega FM, Kunz PL, Liao JC, Leppert JT, Sunwoo JB, Sabatti C, Boehm JS, Hahn WC, Zheng GX, Davis MM, Kuo CJ. Cell. 2018 Dec 13; 175, 1972–1988. Research highlight in Nature Reviews Cancer.

Organoids as Models for Neoplastic Transformation. Neal JT, Kuo CJ. Annu Rev Pathol. 2016 May 23;11:199-220.