Creating a genomic map of the immune response

Dr Sarah Teichmann, Head of Cellular Genetics of the Wellcome Trust Sanger Institute, and Dr Jacqui Shields, from the MRC Cancer Unit in Cambridge, have teamed up to make the most of their complementary skills in immunology and cancer research. Using funding from our Cancer Immunology Project Award, they are focusing on the ‘million dollar question’ often posed by the medical and scientific community: why does the immune system sometimes fail to act against tumour development? Here Sarah describes their project.

The unique value of immunology in cancer research

Sarah and Jacqui are combining expertise from genomics, immunology and dermatology to help solve the complex challenge of how cancer cells can evade the immune system. Sarah explains the approach they are taking:

With the funding from CRUK, we aim to create a map of the immune response against cancer using single cell genomics. We will gather clues from single-cell RNA sequencing data to identify new pathways involved in tumour immunity. We will then validate them experimentally and pre-clinically. We think that understanding the failure of the body’s primary defence system may prove to be instrumental in developing future immunosuppressive targets to prevent this happening.

Bringing together different disciplines

For Sarah, the opportunity to engage with cancer research arose by chance. A year before founding the Single-Cell Genomics Centre at the Wellcome Trust Genome Campus in 2013, she welcomed Bidesh Mahata into her team. During an RNA-sequencing experiment, Bidesh discovered evidence which suggested that immune cells produce immunosuppressive steroids in certain contexts.

From this observation Bidesh proposed that the immune suppression frequently observed within the tumour microenvironment could be driven by immune cell-mediated steroid synthesis.

From there, a cross-disciplinary project was born, adding to Sarah and Jacqui’s expertise was co-investigator and dermatologist, Muzlifah Haniffa.

Since our strengths are in genomics and bioinformatics, this triad of expertise is a dream team for this project.

Their data-driven project aims to unravel the complex choreography of immune cell interactions during a tumour immune response, in the hope of discovering new molecules and cell-driven communications that function under these conditions.

Creating a valuable resource for the immunology community

During the three year study, the team aims to establish the role of steroid-producing immune cells in cancer immune evasion – hopefully ultimately leading to the discovery of one or more immunotherapy targets.

Sarah believes that the genomics data they are gathering from immune cells – whilst the immune response is activated – will be a vital source of information for future cancer research. And when completed, it will be made available through a data portal.

This will be a valuable resource for the cancer immunology community within academia and industry. Researchers will be able to use it in a wider research context to help advance drug development efforts.

Advice for future applicants: focus on an integrative approach

Sarah is complimentary of the Cancer Immunology Project Award funding scheme, and credits her team’s success to their ‘fresh and original’ application that focused on a multidisciplinary and integrative approach.

I had a wonderful experience with the CRUK funding scheme. It was a very smooth process. My advice for any prospective applicant would be that if your projected work is related to cancer-immunology, then keep your fear of failure aside and go for it!