IRISH-1: A retrospective cohort study of PD-L1 by RNA ISH (RISH) as a potentially superior companion biomarker for immune checkpoint inhibitors in NSCLC

The role of the immune system to fight illness is well known, but it can in fact also fight cancer. Indeed, most potential cancer causing cells are detected and removed from our bodies by our immune system in process called "immune surveillance". However, at some point, tumors manage to evade our immune system by producing molecules that inhibit our bodies natural antitumor responses. These are often called "immune checkpoints".

Recent advances in our understanding of these processes has allowed us to develop drugs that can inhibit these checkpoints, a type of treatment known as Immunotherapy. One important immunotherapy involves targeting molecules called "programmed cell death protein 1, or PD1" and "programmed cell death ligand 1, or PD-L1".

Lung cancer is the most common cause of cancer mortality globally, and a major target for immune based therapy. Several drugs that target PD1 have been approved for treating patients with lung cancer, while drugs targeting PD-L1 are now being assessed in several critical clinical trials. However, only about 15-25% of patients will respond to these drugs. This means we must specifically identify the patients who would benefit from these drugs, using a "companion diagnostic" detecting a molecule (often called a biomarker). In this regard, be the appropriate biomarker is considered to be expression of the PD-L1 protein itself, and most studies test for PDL1 with a method called immunohistochemistry, or IHC. However, it has been found that with this test many patients responding to therapy are often negative for PD-L1, and therefore we could be missing patients who might benefit from receiving treatment.

A protein must first come from something called messenger RNA, or mRNA. This project will attempt to see if mRNA for PD-L1 is a better "companion diagnostic" test allowing the detection of more patients capable of benefiting from immunotherapy.

Award Date
30 June 2017
Award Value
Principal Investigator
Dr Steven Gray
Host Institution
Trinity College Dublin
Investigator Led Projects