The Tumour Microenvironment
The tumour microenvironment is an integrated network of various cell types including cancer, stromal, vascular, and immune cells. Tumor cells display aberrant cell growth and signaling patterns to create an environment that favors evasion of the immune system. Such permissive conditions are required for tumor growth, angiogenesis, progression, and metastasis, and immense efforts are underway to understand and counteract these adaptations. However, the complex interplay between cells makes the tumor microenvironment a particularly difficult area of investigation that requires advanced tools for deeper analysis.
Solid tumours are infiltrated by many different types of immune cells; especially the collected tumour infiltrating lymphocytes (TILs). This group includes both mononuclear and polymorphonuclear immune cells, (i.e., CD8+ T cells, B cells, natural killer cells, macrophages, neutrophils, dendritic cells, mast cells, eosinophils, basophils, etc.) in variable proportions. Their abundance varies with tumor type and stage and the presence of lymphocytes in tumors is often associated with better clinical outcomes. Conversely, tumours also contain many different cell types that suppress the anti-tumour immune response. Many cell types are thought to contribute to the generation of an immunosuppressive tumor microenvironment including cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), mesenchymal stem cells, vascular endothelial cells, and lymphatic endothelial cells.
Tools to analyse the tumour microenvironment
Researchers are increasingly turning to techniques that allow visualization of cell types and states in a highly specific and sensitive manner, at the single-cell level and in an intact environment in order to provide morphological context. The RNAscope assay, from ACDbio and In Vitro Technologies, is a valuable approach to visualize and evaluate various cell types and states present in the local tumor environment by detecting key functional molecules such as cytokines and chemokines in addition to cell lineage markers. The RNAscope technology enables rapid and efficient detection of co-expression profiles of any target mRNAs, including checkpoint and cell-specific markers, with single-molecule sensitivity and high specificity in formalin-fixed paraffin-embedded (FFPE) tissues.
The RNAscope assay delivers quantitative, sensitive and specific molecular detection of RNA species on a cell-by-cell basis with morphological context in a robust assay. This enables researchers to visualize which genes are expressed, localize where they are expressed, and quantify the level of expression down to a single transcript of RNA. It is also possible to perform simultaneous detection of target RNA and protein (dual ISH-IHC). This opens up powerful avenues of analysis such as identifying a secreted protein and its cell or origin, or uncovering differential regulation of transcription and translation.
> Learn more about studying the tumour microenvironment with these resources from ACDBio
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Habitat for Disease: Disrupting the Tumor Microenvironment
Unraveling the intricate networks of relationships that make up the tumor microenvironment (TME) are fundamental to developing strategies for preventing disease spread, improving therapeutic efficacy, and overcoming acquired drug resistance. But this complexity also presents unique technical challenges for researchers. In this eBook, uncover reliable solutions, ready resources, and smarter workflows through a breakdown of sought-after answers to key questions for anyone studying the TME.
ACD Webinar Resources
Watch the webinar on "Characterization of immune checkpoint expression & infiltrating immune cells in TME by RNAscope ISH".
Watch the webinar on "Surveying expression of immune checkpoint markers in the tissue microenvironment".
Direct the Immune System by Modulating the Metabolic Pathways that Regulate Cell Fate and Function
Immune cells are highly integrated, relying on a cascade of signaling, networks, and checkpoints to regulate cellular processes. Conventional analytical approaches such as immunophenotyping, cytokine assays, and pathway profiling provide a comprehensive view of immune cell fate and function after the immune cell is committed to a particular outcome. However, pathway intervention and modulation to control immune cell function requires an understanding of the upstream drivers of immune cell processes. Metabolic programs are upstream determinants of immune cell outcomes.
Agilent Seahorse XF technology provides kinetic, functional metabolic measurements for a more direct measure of immune cell processes as they are happening, in real time. To fully understand and control the dynamic nature of immune cell biology, real-time activation analysis is needed to uncover the drivers of activation and provide an opportunity to intervene. Metabolic analysis not only delivers real-time activation kinetics but provides a rich set of pathway targets to modulate immune cell biology.
Webinar: The bioenergetics of immune cell persistence in the tumor microenvironment
In this webinar, Dr. David Ferrick discusses how advances in our understanding of T cell co-receptors have led to new strategies for keeping immune cells turned on in the suppressive, hostile tumor microenvironment. Much has been learned in the last decade about metabolic reprogramming in cancer, focused initially on tumor metabolism. However, by applying this knowledge to infiltrating immune cells we are now beginning to appreciate the metabolic drivers of immune cell fitness, specifically stable mitochondrial function that can perhaps reverse exhaustion phenotypes by enhancing survival and function in hypoxic and nutritionally depleted tumor microenvironments.
Cell Resource
Click on the images below to find out more about other immune cell types.
