@article {1572173,
	title = {Tumor Interferon Signaling Is Regulated by a lncRNA INCR1 Transcribed from the PD-L1 Locus},
	journal = {Mol Cell},
	volume = {78},
	number = {6},
	year = {2020},
	month = {2020 06 18},
	pages = {1207-1223.e8},
	abstract = {Tumor interferon (IFN) signaling promotes PD-L1 expression to suppress T\&nbsp;cell-mediated immunosurveillance. We identify the IFN-stimulated non-coding RNA 1 (INCR1) as a long noncoding RNA (lncRNA) transcribed from the PD-L1 locus and show that INCR1 controls IFNγ signaling in multiple tumor types. Silencing INCR1 decreases the expression of PD-L1, JAK2, and several other IFNγ-stimulated genes. INCR1 knockdown sensitizes tumor cells to cytotoxic T\&nbsp;cell-mediated killing, improving CAR T\&nbsp;cell therapy. We discover that PD-L1 and JAK2 transcripts are negatively regulated by binding to HNRNPH1, a nuclear ribonucleoprotein. The primary transcript of INCR1 binds HNRNPH1 to block its inhibitory effects on the neighboring genes PD-L1 and JAK2, enabling their expression. These findings introduce a mechanism of tumor IFNγ signaling regulation mediated by the lncRNA INCR1 and suggest a therapeutic target for cancer immunotherapy.},
	keywords = {Aged, Animals, B7-H1 Antigen, Cell Line, Tumor, Female, Gene Expression Regulation, Neoplastic, Humans, Immunotherapy, Immunotherapy, Adoptive, Interferon-gamma, Interferons, Janus Kinase 2, Male, Mice, Mice, Inbred NOD, Middle Aged, Programmed Cell Death 1 Ligand 2 Protein, RNA, Long Noncoding, Signal Transduction, STAT1 Transcription Factor, T-Lymphocytes, Cytotoxic},
	issn = {1097-4164},
	doi = {10.1016/j.molcel.2020.05.015},
	author = {Mineo, Marco and Lyons, Shawn M and Zdioruk, Mykola and von Spreckelsen, Niklas and Ferrer-Luna, Ruben and Ito, Hirotaka and Alayo, Quazim A and Kharel, Prakash and Giantini Larsen, Alexandra and Fan, William Y and Auduong, Sophia and Grauwet, Korneel and Passaro, Carmela and Khalsa, Jasneet K and Shah, Khalid and Reardon, David A and Ligon, Keith L and Beroukhim, Rameen and Nakashima, Hiroshi and Ivanov, Pavel and Anderson, Paul J and Lawler, Sean E and Chiocca, E Antonio}
}
