Several recent studies have demonstrated an important role for natural killer (NK) cells in the success of immune checkpoint blockade, in part through the recruitment of type‑1 conventional dendritic cells. Accordingly, there is growing interest in trying to elucidate the mechanisms that mediate the infiltration and activity of innate immune populations.
Recent years have seen a rapid growth in publicly available genomic and transcriptomic data from patient tumour samples. In particular, The Cancer Genome Atlas (TCGA) have generated data from a large number of different cancers, often with matched patient survival data. We recently applied a gene set scoring method, singscore [Foroutan et al. (2018). BMC Bioinformatics], to explore the relative infiltration of NK cells within metastatic melanoma samples. We demonstrated an important role for natural killer cells in promoting patient survival; however, this effect was largely ablated in tumours with evidence of active TGF-β signalling [Cursons/Souza Fonseca Guimaraes et al, (2019), Cancer Immunology Research].
In this seminar I will outline our approach for developing a refined NK cell gene signature, and the use of singscore to estimate NK cell infiltration and interaction effects with different drivers of tumour development and progression, such as TGF- β signalling. I will discuss how we have extended this work to identify putative regulators of innate immune activity, in some cases through the incorporation of single-cell RNA-seq data from dissociated tumours, and how we have been incorporating copy number variation and mutation data to elucidate interactions with immune evasion mechanisms.