Microenvironment Cytometry

It is becoming self-evident that biological systems—from microbes to human tissues—create local microenvironments that can foster survival or impose Darwinian selection that creates unwanted phenotypes. Understanding the dynamic nature of cancer-cell microcommunities in such situations presents a challenge from the conceptual level of cell attractors to the practical level of tracking discrete molecular events and relevant changes by cytometry. There has been a significant increase in the attractiveness of therapeutic strategies that seek to disrupt the ability of neoplastic cells to exploit their microenvironments and present drug-resistant and pro-metastatic phenotypes. Aligned with this is the demand for 3D cellular systems that can mimic aspects of the microenvironment. The chapter discusses methods of cell encapsulation, in particular the application of hollow-fiber technology. Strategies also need to take into account patterns of cellular plasticity and the dynamic heterogeneity in target molecule presentation, especially in co-culture systems. The focus here is on the cytometry of cellular communities within their microenvironments with examples of targeted therapeutic agents. A critical feature of cellular microenvironments, arising from inadequate vascularity, is reduced oxygenation levels. The chapter highlights some of the cellular responses to hypoxia, while research experience suggests that the targeting of hypoxic cells in tumor regions has therapeutic potential.