11 Aug Inflammation is An Important Feature of Uveal Melanoma
MedicalResearch.com Interview with:
Dr. Ulrich Pfeffer
Ulrich Pfeffer, PhD
Laboratory of Molecular Pathology
Istituto di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliera Universitaria San Martino–IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The melanoma of the eye or uveal melanoma is well controlled by radiotherapy or surgery but very aggressively growing metastases often develop and therapy has only marginally improved in decades. On the other hand, uveal melanoma is probably the best studied cancer in absolute: we know its development in great detail and we can make very precise prognosis. An important piece of information that is lacking is the effect of a chromosomal alteration, amplification of a part of chromosome 6, that is often encountered in a subset of uveal melanomas that show features of bad prognosis but actually perform better. Many have guessed that the immune system or more generally, inflammation might protect uveal melanomas with this alteration from progression to metastasis. Therefore we have set out to analyze a candidate gene, the putative immunomodulatory BTNL2, that is located on chromosome 6. We found highly variable expression of this gene in uveal melanoma samples where it is expressed by tumor cells and by infiltrating immune cells. The type of infiltrate is strongly associated with the risk to develop metastases. We also analyzed genetic variants of BTNL2 in 209 patients but we could not find a significant association with uveal melanoma risk.
MedicalResearch.com: What should readers take away from your report?
Response: Inflammation is an important feature of uveal melanoma and BTNL2 is likely to be an important determinant of the local immunological environment.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: BTNL2 is a member of a family of genes that share many features with other immunomodulatory genes. Some of these genes are targets for highly successful therapies. However, many uveal melanoma patients do not respond to these therapies. Future research should address BTNL2 as a specific modulator of the immunological niche of the eye.
MedicalResearch.com: Is there anything else you would like to add?
Response: There is one thing that puzzles me. Our genetic analysis showed a very different frequency of genetic variants than those reported by big genome sequencing projects. We have no explanation for this but it must be considered when dealing with these big data.
There has also been published a commentary to this work: http://archopht.jamanetwork.com/article.aspx?articleid=2542214
This work was possible thanks to a grant from the Italian Association for Cancer Research (AIRC).
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Last Updated on August 12, 2016 by Marie Benz MD FAAD