Global cancer transcriptome quantifies repeat element polarization between immunotherapy responsive and T cell suppressive classes Journal Article
| Authors: | Solovyov, A.; Vabret, N.; Arora, K. S.; Snyder, A.; Funt, S. A.; Bajorin, D. F.; Rosenberg, J. E.; Bhardwaj, N.; Ting, D. T.; Greenbaum, B. D. |
| Article Title: | Global cancer transcriptome quantifies repeat element polarization between immunotherapy responsive and T cell suppressive classes |
| 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. Solovyov et al. compare protocols used in tumor transcriptional profiling. They show the most widely used poly(A) protocol fails to detect several classes of repeat RNAs. In contrast, repeat expression in total RNA sequencing can correlate with the cancer-immune phenotypes and patient responses to immunotherapy. © 2018 The Authors |
| Keywords: | controlled study; human tissue; treatment response; unclassified drug; human cell; antineoplastic agent; colorectal cancer; t lymphocyte; biological marker; phenotype; cancer immunotherapy; gene expression; molecular dynamics; clinical protocol; genetic transcription; prediction; immunotherapy; pancreas tumor; tumor immunity; innate immunity; microenvironment; immune deficiency; genetic code; transcriptome; rna sequence; protein antibody; nucleic acid; clinical outcome; programmed death 1 ligand 1 antibody; rna-seq; polyadenylic acid; cancer immunity; human; priority journal; article; solid malignant neoplasm; repetitive elements; erv; hsatii |
| Journal Title: | Cell Reports |
| Volume: | 23 |
| Issue: | 2 |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press |
| Date Published: | 2018-04-10 |
| Start Page: | 512 |
| End Page: | 521 |
| Language: | English |
| DOI: | 10.1016/j.celrep.2018.03.042 |
| PROVIDER: | scopus |
| PUBMED: | 29642008 |
| PMCID: | PMC6016853 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 May 2018 -- Source: Scopus |
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