lncRNA Regulation of IFNɣ and Its Effect on Checkpoint Inhibitor Expression Enhances Understanding of Therapeutic Cancer Target

In this paper, a cross-institutional team led by the Harvey N. Cushing Neuro-oncology Laboratories (HCNL) at Harvard, explains how checkpoint inhibitors, such as programmed cell death 1 ligand 1 (PD-L1), have introduced a whole new approach to fighting cancer.

The team recently discovered that a poorly characterized long noncoding RNA (lncRNA) — known as Interferon-stimulated Non-Coding RNA1 (INCR1) — regulates IFNɣ signaling of PD-L1.

Specifically, silencing of INCR1 leads to the repression of interferon-stimulated genes (ISG), including PD-L1 which has an inhibitory effect on the cancer-fighting abilities of cytotoxic T cells. When PD-L1 is suppressed, it leaves tumor cells more susceptible to cytotoxic T cells and thus becomes a great target for immunotherapy.

The first step in discovery efforts into regulator effects of INCR1 included whole-transcriptome sequencing (RNAseq) of known cancer cell lines with and without IFNɣ stimulation. Comparison of upregulated lncRNA in the IFNɣ stimulated cells led to all subsequent findings.

Mineo M, Lyons SM, Zdioruk M, von Spreckelsen N, Ferrer-Luna R, Ito H, Alayo QA, Kharel P, Giantini Larsen A, Fan WY, Auduong S, Grauwet K, Passaro C, Khalsa JK, Shah K, Reardon DA, Ligon KL, Beroukhim R, Nakashima H, Ivanov P, Anderson PJ, Lawler SE, Chiocca EA. (2020) Tumor Interferon Signaling Is Regulated by a lncRNA INCR1 Transcribed from the PD-L1 Locus. Mol Cell 78(6):1207-1223.e8. [article]

All RNAseq work was completed at Psomagen Inc. in Rockville, MD USA. Psomagen is a CLIA-certified, CAP-accredited next-generation sequencing services company whose laboratory operations are located within the United States.

For more information on Psomagen, Inc. RNAseq services and research support please visit:


Leave a Reply

Your email address will not be published. Required fields are marked *


Time limit is exhausted. Please reload CAPTCHA.