In a recent study, a group of researchers revealed a protein that is frequently present in lung cancer cells at high levels and that regulates a crucial immunosuppressive pathway that enables lung tumours to avoid immune response (Figure 1). The finding could speed the creation of therapies that defeat this tumour defence mechanism and enhance patient outcomes in lung cancer cases.
The study’s findings, which were supported by analyses of human lung cancer datasets and tests in preclinical lung cancer models, demonstrate that the transcription factor XBP1s promotes tumour survival by inhibiting the anti-tumor activity of nearby immune cells. They found that the synthesis of the potent immunosuppressive chemical prostaglandin E2 is how XBP1s causes this impact.
The unfolded protein response pathway, which is persistently elevated in many malignancies, was the focus of the study’s attention. It consists of the IRE1-XBP1 arm. Other tumour types have been the subject of investigations in the past, and it has been demonstrated that this route not only directly encourages the survival and growth of tumours but also works to limit the antitumor activity of adjacent immune cells.
The gene activity “signature” resulting from IRE1 knockout in mouse non-small cell lung cancer (NSCLC) tumours was also mapped as part of the work. They discovered that this gene signature’s presence in human NSCLC tumours predicted improved patient survival.
They suggested that in the future, a clinical test based on this signature would be helpful for prognosticating outcomes and choosing the best therapies.
Journal article: Crowley, M.J.P., et al., 2023. Tumour-intrinsic IRE1α signaling controls protective immunity in lung cancer. Nature Communications.
Summary by Stefan Botha