Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Professor Yang Shi’s group uses combination therapy to eradicate tumours that previously responded poorly to immunotherapy

An animated drawing of a syringe releasing contents that attacks cancer cells

Immunotherapy has shown remarkable efficacy against a range of cancers. One approach, termed immune checkpoint blockade therapy, blocks an inhibitory immune receptor called PD-1 to take the brakes off the immune system and allow it to kill cancer cells. However, despite this success, anti-PD-1 therapy is ineffective in the majority of cancer patients.

Research is underway to discover strategies that can overcome tumour resistance to immunotherapy. A promising avenue for further investigation is the manipulation of epigenetic regulators. Epigenetic regulators influence the expression of genes without changing the underlying DNA sequence. They can dampen the response of the immune system and their inhibition has been shown to enhance the response to anti-PD-1 treatment. However, because epigenetic regulators are involved in several aspects of the anti-tumour immune response, inhibiting them can result in potentially opposing effects, with the result of little or no overall benefit.

In this paper published in the journal Cancer DiscoveryProfessor Yang Shi and his laboratory explore the opposing effects of inhibiting one such epigenetic regulator, LSD1. Using mouse and tumour cell models, they show that when LSD1 is repressed, there is a greater immune cell infiltration into the tumour but this is counteracted by the increased production of a cell regulatory protein called TGF-β that suppresses the ability of these infiltrating immune cells to kill cancer cells.

To tackle these conflicting effects, the team experimentally depleted both LSD1 and TGF-β during anti-PD-1 therapy and demonstrated a significant increase in immune cell infiltration, cytotoxicity and cancer cell killing. This combination treatment led to eradication of these previously resistant tumours and long-lasting protection from tumour re-challenge, making it a promising future strategy for increasing the efficacy of this important class of cancer treatment.

Similar Stories

Applied mathematical principles help identify immune cell spatial patterns in tumours

A collaboration between mathematicians, pathologists and clinicians has shown how techniques from computational algebraic topology can be used to understand the spatial distributions of immune cell subtypes within tumours.

Haematology workshops enable significant patient involvement

The 'What Matters Most’ initiative was designed as a way of bringing people with Myelodyspastic Syndrome together to talk about their shared experience, and agree a list of priorities for research and service / resource development.

Anti-cancer drug derived from fungus shows promise in clinical trials

A new industry-academic partnership between the University of Oxford and biopharmaceutical company NuCana as found that chemotherapy drug NUC-7738, derived from a Himalayan fungus, has 40 times greater potency for killing cancer cells than its parent compound.