Global Cancer Transcriptome Quantifies Repeat Element Polarization Between Immunotherapy Responsive and T Cell Suppressive Classes

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2018 Apr 12

PMID 29642008

Citations 58

Authors

Alexander Solovyov

Nicolas Vabret

Kshitij S Arora

Alexandra Snyder

Samuel A Funt

Dean F Bajorin

Jonathan E Rosenberg

Nina Bhardwaj

David T Ting

Benjamin D Greenbaum

Affiliations

Soon will be listed here.

Abstract

It has been posited that anti-tumoral innate activation is driven by derepression of endogenous repeats. We compared RNA sequencing protocols to assess repeat transcriptomes in The Cancer Genome Atlas (TCGA). Although poly(A) selection efficiently detects coding genes, most non-coding genes, and limited subsets of repeats, it fails to capture overall repeat expression and co-expression. Alternatively, total RNA expression reveals distinct repeat co-expression subgroups and delivers greater dynamic changes, implying they may serve as better biomarkers of clinical outcomes. We show that endogenous retrovirus expression predicts immunotherapy response better than conventional immune signatures in one cohort yet is not predictive in another. Moreover, we find that global repeat derepression, including the HSATII satellite repeat, correlates with an immunosuppressive phenotype in colorectal and pancreatic tumors and validate in situ. In conclusion, we stress the importance of analyzing the full spectrum of repeat transcription to decode their role in tumor immunity.

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