Molecular and pharmacological modulators of the tumor immune contexture revealed by deconvolution of RNA-seq data

ABSTRACT The immune contexture has a prognostic value in several cancers and the study of its pharmacological modulation could identify drugs acting synergistically with immune checkpoint blockers. However, the quantification of the immune contexture is hampered by the lack of simple and efficient methods. We developed quanTIseq, a deconvolution method that quantifies the densities of ten immune cell types from bulk RNA sequencing data and tissue imaging data. We performed extensive validation using simulated data, flow cytometry data, and immunohistochemistry data from three cancer cohorts. Analysis of 8,000 samples showed that the activation of the CXCR3/CXCL9 axis, rather than the mutational load is associated with cytotoxic T cell infiltration. We also show the prognostic value of deconvolution-based immunoscore and T cell/B cell score in several solid cancers. Finally, we used quanTIseq to show how kinase inhibitors modulate the immune contexture, and we suggest that it might have predictive value for immunotherapy.