Scientists at the University of Turku in Finland have developed a new preclinical model that could accelerate the development of therapies for aggressive melanomas that are highly resistant to current immunotherapies.

The model focuses on BAP1-deficient melanoma, a rare and particularly aggressive form of melanoma that suppresses the immune system after metastasis and fails to respond to modern immune checkpoint inhibitors. Although uncommon, metastatic BAP1-deficient melanoma is the most frequent primary cancer of the eye in adults. Once the disease spreads—especially to the liver, which occurs in about half of patients—survival is typically limited to only a few months.

Researchers identified the loss of the BAP1 (BRCA1-associated protein 1) gene as the main factor driving tumor progression and immune evasion. Without this gene, tumors grow more rapidly and prevent immune cells from attacking cancer. BAP1 loss is also implicated in several other difficult-to-treat cancers, including mesothelioma and kidney cancer.

Until now, scientists lacked an effective laboratory model capable of accurately reproducing the interaction between these tumors and the immune system, making it difficult to investigate new treatment strategies.

To overcome this challenge, the research team used CRISPR-Cas9 gene-editing technology to remove the BAP1 gene from healthy melanocyte cells. The resulting model closely mimics the behavior of human BAP1-deficient melanoma while preserving a fully functional immune system in laboratory animals.

According to lead researcher Dr. Mona Wang Meng, the model is the first to faithfully recreate the tumor immune microenvironment observed in patients, providing researchers with a valuable platform for investigating how BAP1 loss enables tumors to escape immune surveillance and for testing innovative immunotherapy combinations designed to overcome treatment resistance.

The researchers note that the new platform has applications beyond melanoma. Since BAP1 mutations are found in several aggressive cancers, the model could support the development of novel immunotherapies across multiple tumor types.

The findings were published in the journal Communications Biology.