Publications by authors named "Ileana L Co"

Understanding the highly complex tumor-immune landscape is an important goal for developing novel immune therapies for solid cancers. To this end, 3D cancer-immune models have emerged as patient-relevant in vitro tools for modeling the tumor-immune landscape and the cellular interactions within it. In this review, we provide an overview of the components and applications of 3D cancer-immune models and discuss their evolution from 2015 to 2023.

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The spatial configuration of cells in the tumor microenvironment (TME) affects both cancer and fibroblast cell phenotypes contributing to the clinical challenge of tumor heterogeneity and therapeutic resistance. This is a particular challenge in stroma-rich pancreatic ductal adenocarcinoma (PDAC). Here, a versatile system is described to study the impact of tissue architecture on cell phenotype using PDAC as a model system.

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Article Synopsis
  • - The aryl hydrocarbon receptor (AhR) plays a crucial role in immune modulation and is significantly active in tumor-associated macrophages (TAMs) within pancreatic ductal adenocarcinoma (PDAC).
  • - Deleting or inhibiting AhR in macrophages led to decreased PDAC tumor growth, enhanced response to immune therapies, and increased CD8 T cell activity, independent of tryptophan metabolism within the macrophages.
  • - In patients with PDAC, higher AhR levels correlated with worse outcomes and a suppressive immune environment, indicating that AhR regulation could be a critical factor in the disease's progression.
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Omics technologies, such as genomics, epigenomics, transcriptomics, proteomics, metabolomics, lipidomics, multiomics, and integrated modalities, have greatly contributed to our understanding of various diseases by enabling researchers to probe the molecular wiring of cellular systems in a high-throughput and precise manner. With the development of tissue-engineered three-dimensional (3D) disease models, such as organoids and spheroids, there is potential of integrating omics technologies with 3D disease models to elucidate the complex links between genotype and phenotype. These 3D disease models have been used to model cancer, infectious disease, toxicity, neurological disorders, and others.

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Brain organoids are self-assembled, three-dimensionally structured tissues that are typically derived from pluripotent stem cells. They are multicellular aggregates that more accurately recapitulate the tissue microenvironment compared to the other cell culture systems and can also reproduce organ function. They are promising models for evaluating drug leads, particularly those that target neurodegeneration, since they are genetically and phenotypically stable over prolonged durations of culturing and they reasonably reproduce critical physiological phenomena such as biochemical gradients and responses by the native tissue to stimuli.

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