Some of the mysteries of uveal melanoma revealed by UMCure2020 researchers: the importance of BAP1 mutation on the immune profile.

Loss of BAP1 expression leads to a suppression of the immune response to UM, with implications for immunotherapy development

 

One of the most common mutations that initiates UM devellopemnt occurs in the gene coding for the BRCA1-associated protein (BAP1). The BAP1 gene is mutated in almost 50% of all UM cases and associated with high risk tumours – tumours with high chances of producing metastatic disease.

The exact process by which the loss of BAP1 gene leads to the creation of more aggressive tumours is still unknown. This study by Dr. Carlos Figueiredo and the Liverpool Ocular Oncology Research Group sheds some light on the mechanisms behind it.

Immunotherapy works by empowering the immune system to fight cancer cells. One of the reasons that immunotherapies fail to treat metastatic UM is that, for the majority of UM cases, the patients’ immune system fails to recognize the tumour.

Prof. Sarah Coupland’s Lab identified alterations on UM cancer cells, induced by the loss of BAP1 gene, that suppress a protective immune response. In other words, the absence of the BAP1 gene appears to make UM immune to the immune system itself.

However, recent treatment developments with drugs like tebentafusp (that marks UM cancer cell making them recognizable to the immune system), adoptive cell therapy using tumour infiltrating lymphocytes (a treatment based on “trainning” white blood cells to be more effective in targeting cancer cells) and isatuximab (which disables one of the mechanisms that cancer cells have to halt the immune response) may provide a solution for managing metastatic uveal melanoma that is currently unresponsive to traditional immunotherapy, being further clinical studies needed to establish their efficacity.

You can read the original paper here.