Skip to main content
Publications of the Week

Assessment of Long Non-Coding RNA Expression Reveals Novel Mediators of the Lung Tumour Immune Response

By October 21, 2020October 26th, 2020No Comments

Read the Publication

This week we profile a recent publication in Scientific Reports from Adam Sage
and Erin Marshall (pictured) in the laboratory of Dr. Wan Lam at BC Cancer.

Can you provide a brief overview of your lab’s current research focus?

The Lam Lab currently focuses on genetic and genomic methods of discovering new cancer drivers, in particular in lung cancer. Wan’s team develops novel whole genome technologies and bioinformatics methodologies for tracking genetic, epigenetic, and gene expression changes in order to identify genes that govern cancer progression and treatment responses. The major pillars of discovery that the lab is focuses on include understanding the lung tumour microenvironment in cancer initiation and progression, understanding environmental factors that lead to lung cancer, and assessing the contribution of other comorbidities to lung cancer development, including COPD.

What is the significance of the findings in this publication?

Long non-coding RNAs (lncRNAs) have emerged as key modulators of tumour development, progression, and response to therapy across a variety of cancer types. Here, we examine lncRNA expression in separate sequencing cohorts, including single-cell and bulk RNA sequencing data from lung tumours, matched adjacent normal tissue, and flow-sorted healthy immune cell subsets, to characterize the landscape of lncRNAs expressed in tumour-infiltrating lymphocytes in a highly immunogenic tumour type. We find previously-undescribed lncRNAs expressed in cytotoxic T cells and natural killer (NK) cells that correlate with patient outcome and immune infiltrate, and further characterize a lncRNA upregulated in NK cells stimulated in vitro which regulates expression of the well-known cytotoxic gene NKG7. Strikingly, knockdown of this lncRNA impaired NK cell-dependent killing of lung tumour cells, demonstrating that dysregulation of immune cell-derived lncRNAs can functionally influence anti-lung tumour immunity.

Our study provides insight into tumour cell-extrinsic lncRNAs detectable in bulk RNAseq data, and cautions that components of the tumour microenvironment, including but not limited to infiltrating immune cells, may confound analysis of bulk tumour data. However, technical advances in sequencing technologies should aid in accurate mapping of transcripts to their cell of origin. Nevertheless, we show that these ‘contaminants’ in tumour expression profiles not only serve as useful biomarkers for patient outcome, but also functionally contribute to anti-tumour immune responses.

What are the next steps for this research?

As these observations demonstrate the impact of lncRNA deregulation on the cytotoxic activity of anti-tumour cells, we next aim to explore how impaired lncRNA expression and subsequent disruption of important gene-regulatory pathways as a mechanism of tumour immune system evasion.

This work was funded by:

This work was supported by the Canadian Institutes for Health Research.

Read the Publication