Abstract
Recent advances in single-cell transcriptomics have greatly improved knowledge of complex transcriptional programs, rapidly expanding our knowledge of cellular phenotypes and functions within the tumour microenvironment and immune system. Several new single-cell technologies have been developed over recent years that have enabled expanded understanding of the mechanistic cells and biological pathways targeted by immunotherapies such as immune checkpoint inhibitors, which are now routinely used in patient management with high-risk early-stage or advanced melanoma. These technologies have method-specific strengths, weaknesses and capabilities which need to be considered when utilising them to answer translational research questions. Here, we provide guidance for the implementation of single-cell transcriptomic analysis platforms by reviewing the currently available experimental and analysis workflows. We then highlight the use of these technologies to dissect the tumour microenvironment in the context of cancer patients treated with immunotherapy. The strategic use of single-cell analytics in clinical settings are discussed and potential future opportunities are explored with a focus on their use to rationalise the design of novel immunotherapeutic drug therapies that will ultimately lead to improved cancer patient outcomes.
Highlights
Tumours are made up of a complex mixture of proliferating malignant cells, immune cells, blood vessels and tumour stroma (Figure 1) [1,2,3]
We summarise the landscape of commonly used single-cell and spatial transcriptomic technologies in cancer research, whilst discussing their advantages and shortcomings in terms of their capture efficiency, cell restriction, spatial resolution, and analytical support
We outline the following single-cell transcriptomic platforms including 10x Chromium, Fluidigm C1, and SMART-seq2, that have been widely used in the field of cancer research, providing a summarised guide that can assist a broad range of biomedical researchers to make an informed decision for their single-cell studies
Summary
Tumours are made up of a complex mixture of proliferating malignant cells, immune cells, blood vessels and tumour stroma (Figure 1) [1,2,3]. Current approaches for single-cell analysis using immunohistochemistry, in-situ hybridisation, and flow cytometry have been essential tools for detecting the differences between non-malignant cells and cancer cells in the laboratory, as well as in the clinic [21,22,23,24] These conventional methods examine individual cells and dissect the different subtypes of cells in the tumour and complement bulk-based genomic analysis [4,25]. Single-cell approaches offer great potential to answer many clinically and biologically important questions that persist in cancer research, including: the contribution of TME and tumour heterogeneity to evade the anti-tumour response; the temporal relationship between T cell clonotype and tumour cells during treatment; the interacting network of immune checkpoint molecules in TME; and the functional roles and spatial relationships between tumour cell subtypes and immune cells [43,44,45,46,47]. We discuss the advances made using single-cell techniques in healthcare and clinical research
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