Researchers have created a powerful new cell model to study rare tumors that are resistant to immunotherapy. This tool could change the way treatments are developed for melanoma, for which there are currently few effective treatment options.
A research team at the University of Turku in Finland has developed a reliable laboratory model to study BAP1-deficient melanoma. BAP1-deficient melanoma is a rare type of melanoma that evades the immune system once it metastasizes and is universally resistant to current state-of-the-art immunotherapies.
Metastatic BAP1-deficient melanoma is the most common intraocular malignancy in adults, but it remains rare and extremely difficult to treat once it has spread. Once the disease reaches the liver, as it does in about half of patients, median survival is measured in months. Unlike common melanomas, BAP1-deficient melanomas do not respond to immune checkpoint therapies that have transformed cancer treatment over the past decade.
The main factor behind tumor immune evasion is the loss of a gene called BAP1 (BRCA1-associated protein 1). Loss of BAP1 makes tumors more aggressive, grows faster, and suppresses immune cells that attack tumors. Loss of BAP1 is the most important molecular event in the progression of uveal melanoma and is also involved in mesothelioma, renal cell carcinoma, and other cancers.
However, due to the lack of a suitable immunocompetent model, scientists have not been able to properly study the effects of BAP1 loss in the laboratory.
Gene editing solved the missing piece of the puzzle
To address this issue, the research team used CRISPR-Cas9 gene editing to delete BAP1 from normal melanocyte cells, creating a new preclinical tumor model that behaves like human BAP1-deficient melanoma in animals with fully functional immune systems.
BAP1 deficiency is associated with poor prognosis and resistance to immunotherapy in melanoma. Until now, no preclinical model existed that faithfully reproduced the tumor-immune interactions seen in patients. Our model fills this gap for the first time by recapitulating the immune microenvironment of human tumors in vivo. This provides a powerful platform to study how BAP1 deficiency causes immune evasion and test new immunotherapeutic combinations that may overcome treatment resistance. ”
Dr. Mona Wang Meng, Research Principal Researcher, University of Turku
The lack of appropriate clinical testing models remains one of the biggest bottlenecks slowing down drug development for BAP1-deficient melanoma and related rare tumors. Previous models either lacked a functional immune system to be unhelpful for immunotherapy studies or had too many confounding mutations that obscured the specific role of BAP1.
“The impact extends far beyond melanoma. BAP1 deficiency is a common vulnerability in several difficult-to-treat cancers. This platform allows us and research groups around the world to rationally design and test new immunotherapy combinations that were previously not possible,” said Carlos R. Figueiredo, Ph.D., principal investigator of the study.
The study was published in the journal Communication biology. This is part of MIORG’s broader research program within the InFLAMES research flagship at the University of Turku, which focuses on harnessing the immune system to fight cancer.
sauce:
University of Turku
Reference magazines:
Mr. Wang, Mr. MM, Others. (2026). A novel CRISPR-Cas9 BAP1 knockout preclinical tumor model recapitulates tumorigenesis and immune evolution of human melanoma. communication biology. https://www.nature.com/articles/s42003-026-10118-x
