Dysregulated Repeat Element Viral-like Immune Response in Hepatocellular Carcinoma.

Autor:	Coley AK; Mass General Cancer Center, Harvard Medical School; Charlestown, MA, USA.; Department of Surgery, Massachusetts General Hospital Harvard Medical School; Boston, MA, USA., Lu C; Mass General Cancer Center, Harvard Medical School; Charlestown, MA, USA.; Health Sciences and Technology Program; Cambridge, MA, USA., Pankaj A; Mass General Cancer Center, Harvard Medical School; Charlestown, MA, USA., Emmett MJ; Mass General Cancer Center, Harvard Medical School; Charlestown, MA, USA.; Department of Medicine, Massachusetts General Hospital, Harvard Medical School; Boston, MA, USA., Lang ER; Mass General Cancer Center, Harvard Medical School; Charlestown, MA, USA., Song Y; Mass General Cancer Center, Harvard Medical School; Charlestown, MA, USA., Xu KH; Mass General Cancer Center, Harvard Medical School; Charlestown, MA, USA., Xu N; Mass General Cancer Center, Harvard Medical School; Charlestown, MA, USA., Patel BK; Mass General Cancer Center, Harvard Medical School; Charlestown, MA, USA., Chougule A; Mass General Cancer Center, Harvard Medical School; Charlestown, MA, USA., Nieman LT; Mass General Cancer Center, Harvard Medical School; Charlestown, MA, USA., Aryee MJ; Department of Biostatistics, Harvard T.H. Chan School of Public Health; Boston, MA, USA.; Department of Data Sciences, Dana-Farber Cancer Institute; Boston, MA, USA.; Broad Institute of Harvard and MIT; Cambridge, MA, USA., Ferrone CR; Department of Surgery, Cedars-Sinai Hospital; Los Angeles, CA, USA., Deshpande V; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School; Boston, MA, USA., Franses JW; Mass General Cancer Center, Harvard Medical School; Charlestown, MA, USA.; Department of Medicine, Massachusetts General Hospital, Harvard Medical School; Boston, MA, USA.; Health Sciences and Technology Program; Cambridge, MA, USA.; Section of Hematology-Oncology, Department of Medicine, University of Chicago; Chicago, IL, USA., Ting DT; Mass General Cancer Center, Harvard Medical School; Charlestown, MA, USA.; Department of Medicine, Massachusetts General Hospital, Harvard Medical School; Boston, MA, USA.; Health Sciences and Technology Program; Cambridge, MA, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Dec 05. Date of Electronic Publication: 2023 Dec 05.
DOI:	10.1101/2023.12.04.570014
Abstrakt:	Purpose: Dysregulation of viral-like repeat RNAs are a common feature across many malignancies that are linked with immunological response, but the characterization of these in hepatocellular carcinoma (HCC) is understudied. In this study, we performed RNA in situ hybridization (RNA-ISH) of different repeat RNAs, immunohistochemistry (IHC) for immune cell subpopulations, and spatial transcriptomics to understand the relationship of HCC repeat expression, immune response, and clinical outcomes. Experimental Design: RNA-ISH for LINE1, HERV-K, HERV-H, and HSATII repeats and IHC for T-cell, Treg, B-cell, macrophage, and immune checkpoint markers were performed on 43 resected HCC specimens. Spatial transcriptomics on tumor and vessel regions of interest was performed on 28 specimens from the same cohort. Results: High HERV-K and high LINE1 expression were both associated with worse overall survival. There was a positive correlation between LINE1 expression and FOXP3 T-regulatory cells (r = 0.51 p < 0.001) as well as expression of the TIM3 immune checkpoint (r = 0.34, p = 0.03). Spatial transcriptomic profiling of HERV-K high and LINE-1 high tumors identified elevated expression of multiple genes previously associated with epithelial mesenchymal transition, cellular proliferation, and worse overall prognosis in HCC including SSX1, MAGEC2, and SPINK1. Conclusion: Repeat RNAs may serve as useful prognostic biomarkers in HCC and may also serve as novel therapeutic targets. Additional study is needed to understand the mechanisms by which repeat RNAs impact HCC tumorigenesis. Competing Interests: COMPETING INTERESTS STATEMENT DTT has received consulting fees from ROME Therapeutics, Sonata Therapeutics, and Tekla Capital. DTT is a founder and has equity in ROME Therapeutics, PanTher Therapeutics and TellBio, Inc., which is not related to this work. DTT is on the advisory board for ImproveBio, Inc. DTT has received honorariums from Moderna and Ikena Oncology that are not related to this work. DTT receives research support from ACD-Biotechne, AVA LifeScience GmbH, and Incyte Pharmaceuticals, which was not used in this work. DTT’s interests were reviewed and are managed by Massachusetts General Hospital and Mass General Brigham in accordance with their conflict-of-interest policies.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu