Discovery Could Make Cancer Immunotherapy More Effective

Southampton scientists working to improve survival for cancer patients have identified a key characteristic of the disease that could make treatment more effective.

The aim of the University of Southampton study, funded by Cancer Research UK and Gilead Sciences Inc, is for patients to respond better to immunotherapy. This is a treatment that supercharges the body’s immune system to kill cancer cells.

Many patients do not respond well to immunotherapy, said Professor Gareth Thomas who led the £1.4million study and has been examining the types of cells that surround tumours – cancer associated fibroblasts (CAFs).

It aimed to find out what stops the treatment from working and if there are any characteristics that could be enhanced to make it work more effectively.

Using tissue samples donated by patients from Poole General Hospital, the team used sequencing technology that analyses individual cells in cancers.

The researchers identified a different type of fibroblast that may help the body’s immune system attack tumours. It’s now hoped this feature could be replicated in patients’ cancers to make immunotherapy work more effectively.

Professor of Experimental Pathology Gareth Thomas said: “We have spent a long time studying the types of cells that stop immunotherapy from working properly, and we already knew there was a certain type of cancer-associated fibroblast that blocks the body’s anti-tumour immune response.

“In this study, we decided to do the opposite, and try to get a better understanding of cells that actively support anti-tumour immunity. To do this we started by analysing head and neck cancers caused by human papillomavirus (HPV), a type of cancer known to produce a strong immune response that is associated with longer survival.

“Excitingly, in these cancers we found a type of fibroblast that we think helps stimulate anti-cancer immunity. We also found this cell in other cancer types and have shown that patients whose cancers contain lots of these cells have a much better response to immunotherapy.

“Our team has worked out what makes these cells form and can now do this in the lab. Our next step is to work out whether we can use this information to develop a treatment that supercharges a patient’s response to cancer immunotherapy, giving them a better chance of beating this disease.”

The study has been published by Molecular Cancer and can be found here .

Cancer Research UK’s executive director of research and innovation, Iain Foulkes, said: “Immunotherapy is a promising area for the treatment of many cancers, but resistance to immunotherapy remains common. Knowing there is a chance some treatments may not work can be hard for some patients who may experience side effects whilst receiving them.

“Research like this, that offers insights into how we could improve their response to immunotherapy across multiple cancer types is an exciting development and we hope it could lead to better chances for patients undergoing these types of treatments.”

Reference: Jenkins BH, Tracy I, Rodrigues MFSD, et al. Single cell and spatial analysis of immune-hot and immune-cold tumours identifies fibroblast subtypes associated with distinct immunological niches and positive immunotherapy response. Mol Cancer. 2025;24(1):3. doi:10.1186/s12943-024-02191-9

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