Abstract
While tools to study cells and molecules from tissue samples have provided important knowledge about the function of the immune system in health and disease, many have required the extraction of these cells from their normal environment. More recent technologies, in partnership with existing imaging platforms, have allowed the study of cells and molecules in situ. This approach allows the study of not just the heterogeneity of the immune response, but also the plasticity of immune cells. The latter is important because immune cell function is significantly influenced by the cellular neighbourhood – immune, stromal or tumour cells, secreted molecules, structural components such as vasculature, and the ability to make cell-cell contact. These new tools have allowed us to look at structures within the body, especially in human tissues, and have provided new biological information on immune function, as well as new ways to predict disease outcomes. Many of these studies have been initially carried out in the context of the tumour microenvironment (TME). Cohn et al. review the importance of multiple factors in the TME and the tumour immune microenvironment (TIME) that have a known effect on patient outcome and which, therefore, need to be studied in their local surroundings. These authors highlight the role of cancer-derived factors, bacteria, and other immune cells in affecting patient outcome, and review how interactions between these factors and local immune cells are likely to direct these outcomes. These interactions also represent potential biomarkers of disease progression. Cohn et al. provide a comprehensive review of current imaging techniques, from traditional histochemistry-based approaches to sophisticated multi-parameter protein and RNA analyses. They highlight strengths and limitations of each technique and provide examples of key findings from each approach that have contributed to fundamental knowledge about the immune system in cancer. For any researcher considering spatial analysis of tissues, this paper provides a superb starting point to determine experimental and analytical approaches based on their specific research question. Two examples of imaging technology and the importance of space and associated structures are provided by Moamin et al. and Femel et al. Moamin et al. use a simple multiplex immunohistochemistry (mIHC) approach to study immune cell phenotypes in triple negative breast cancer. Importantly, they study these phenotypes in the context of perivascular areas within the TME. They show that tumour-associated macrophages Frontiers in Immunology