RT Journal Article
SR Electronic
T1 Molecular and pharmacological modulators of the tumor immune contexture revealed by deconvolution of RNA-seq data
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 223180
DO 10.1101/223180
A1 Francesca Finotello
A1 Clemens Mayer
A1 Christina Plattner
A1 Gerhard Laschober
A1 Dietmar Rieder
A1 Hubert Hackl
A1 Anne Krogsdam
A1 Zuzana Loncova
A1 Wilfried Posch
A1 Doris Wilflingseder
A1 Sieghart Sopper
A1 Marieke Ijsselsteijn
A1 Douglas Johnson
A1 Yaomin Xu
A1 Yu Wang
A1 Melinda E. Sanders
A1 Monica V. Estrada
A1 Paula Ericsson-Gonzalez
A1 Justin Balko
A1 Noel de Miranda
A1 Zlatko Trajanoski
YR 2018
UL http://biorxiv.org/content/early/2018/08/17/223180.abstract
AB 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.