Within the tumor microenvironment (TME), cancer cells intermingle with immune cells, blood vessels, and various tissue cells, forming a protective barrier against the immune system and drug penetration. Exploring the TME with spatial biology holds promise for uncovering strategies to alter this environment and combat cancer.
Download this poster from Drug Discovery News to learn about different spatial profiling techniques and discover how they reveal novel insights into tumor heterogeneity.
By Angela Zhang, PhD Designed by Jerry Mensah
Cancer is driven by alterations to the genome and epigenome. The heterogeneous composition of tumors and their propensity to change over time demand that scientists look at the spatial context of cancer biology to make the next discovery.
The tumor microenvironment (TME) consists of cancer cells along with structural tumor cells, blood vessels, immune cells, and other tissue cells unique to the type of tumor. The TME promotes tumor growth and survival and creates an immunosuppressive environment that shields the tumor from the immune system and prevents drug entry (1). Exploring the tumor microenvironment with spatial biology may reveal how scientists can hijack this space to a patient’s advantage. Scientists use three major spatial biology techniques to study the TME.
Scientists integrate genes that encode fluorescent proteins into the genomes of early cancer cells, allowing them to visualize how these cells organize and move around the TME (1). This multiplex technique, called optical clonal barcoding, led to the discovery of key biomarkers for instead of recurring head and neck squamous cell carcinoma (2).
Spatial proteomics captures the dynamic localization of proteins in and around the cells of the TME. For multiplex spatial proteomics, a collection of fluorescently-labeled antibodies bind to different proteins in the TME. Scientists then visualize the bound antibodies with mass spectrometry or fluorescence imaging (1).
Fluorescence in situ hybridization deduces protein expression based on spatial RNA profiling. RNA probes with attached fluorophores bind to areas in the TME where a specific mRNA transcript is expressed (1). By detecting fluorescence, researchers determine unique gene expression patterns, including those that predict drug resistance (3). New in situ hybridization technologies sequence mRNA transcripts directly from tissue samples, helping scientists resolve gene expression and better understand the TME.
References
1. Lewis, S.M., Asselin-Labat, ML., Nguyen, Q. et al. Spatial omics and multiplexed imaging to explore cancer biology. Nat Methods 18, 997–1012 (2021).
2. Roh, V. et al. Cellular barcoding identifies clonal substitution as a hallmark of local recurrence in a surgical model of head and neck squamous cell carcinoma. Cell Rep 25, 2208–2222 (2018).
3. Shaffer, S. M. et al. Rare cell variability and drug-induced reprogramming as a mode of cancer drug resistance. Nature 546, 431–435 (2017).