Deciphering the connection of genetics, immune infiltration and prognosis

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Published: 12 May 2017
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Dr Jan Budczies - Charité Universitätsmedizin Berlin, Berlin, Germany

Dr Budczies speaks with ecancer at IMPAKT 2017 about immune surveillance and escape in breast cancer.

He reports on bioinformatic interrogation of tumour data from The Cancer Genoma Atlas, identifying tumour-infiltrating lymphocyte activity and their role in 'hot' tumours.

Dr Budczies looks towards further analysis and identification of biomarkers that may predict checkpoint therapy response.

Cancer genomics and immune response were discussed further at IMPAKT 2017 by Prof Fabrice André.

Can you tell us about your current research?

Yes, a lot of questions in this direction are unresolved, that’s why I’m doing research on that. The tumour genetics make new kinds of changed proteins and these proteins can be recognised by the immune system. This could depend on what mutations you have if the tumour can be recognised by the immune system but the way around the functional or non-functional immune system also may influence which kinds of tumour cells can survive. So if immune surveillance doesn’t work possibly a lot of different clones can appear and the immune system can no longer eliminate these clones.

How did you conduct your research?

I’m a bioinfomatician so I’m looking to this question, to this immune oncology question, from the perspective of high throughput data like NGS data and gene expression data. In the work I presented here I analysed data from the Cancer Genome Atlas where we have all this data but we also have H&E slides where pathologists can do quantification of tumour infiltrating lymphocytes, TILs.

What did you find in your research?

I could reproduce the findings that in certain molecular subtypes of breast cancer, for example the triple negative breast cancer, you have more immune infiltrates. I can measure this by TILs and I also can measure this by specific markers of mRNA which can give me more specific information about different kinds of lymphocytes like T-cells for example. What I also studied is I looked if I have the TILs that are determined from the slides with which genes are correlating most with this. The result was that typical T-cell markers like CTLA-4, for example, have a high correlation with the TILs.

What are the potential clinical implications?

This is a contribution to understand more about the interaction between the genetics and the immune system and to single out immunological hot tumours and maybe to make a more quantitative or to look if there could be different kinds of lymphocyte. That’s why I looked for T-cells, B-cells and neutrophils and other kinds of immune cells in these tumours. I hope this can contribute to a better selection of patients for immune therapy.

What is next for your research?

What will be next in my research? I would like to look if these markers I investigate here if I can apply it in patients that are treated by immune checkpoint inhibitors and if some of these markers are possibly predictive if this immune therapy helps. So I want to look in clinical trials where immune therapies are tested and analysed, do biomarker analysis in these trials.