Despite continued advances in cancer research, 50% of patients with uveal or ocular melanoma continue to develop metastases. It is a rare type of melanoma, but it is the most common intraocular cancer in adults and has a great tendency to spread, especially in the liver. Now, taking another step forward in improving the treatment of this type of cancer, a group of researchers from several European centres, including Dr. Josep Maria Piulats, co-leader of the Cancer Immunotherapy research group at  IDIBELL and ICO, and the medical oncologist and researcher at ICO-IDIBELL, Luis del Carpio, has published a study in Nature Communications in which they show promising results to improve the therapy of metastatic uveal melanoma.

Immunotherapy for uveal melanoma

The research has focused on the study of tebentafusp, an immunotherapy drug that has shown remarkable efficacy in improving the survival of certain patients with metastatic uveal melanoma. The mechanism of action of this drug is based on facilitating the encounter between immune cells and tumour cells: it takes the body’s defences to the core of the cancer. It is an antibody designed to bind, on the one hand, to T lymphocytes and, on the other hand, to a tumor-specific protein, building a molecular bridge through which T cells can detect the tumor and destroy it.

However, the tumour immune microenvironment, the dynamic set of cells and molecules that surround the tumour, has a decisive influence on the success of these immunotherapies, whether positive or negative. Tumor-associated macrophages, immune system cells that play a key role in defending the body against infections, are among the most abundant immune populations in this microenvironment and, although not always, are often associated with significant inhibition of T cells. In fact, this is the role they seem to play in metastatic uveal melanoma, and may decisively affect the efficacy of tebentafusp therapy.

A complex cellular interaction at the heart of the tumor

Based on what they have seen in vitro, the researchers of this study have been able to corroborate that there is a type of macrophage (M2) in the microenvironment of uveal melanoma that inhibits the activity of T cells, thus reducing the effectiveness of tebentafusp. Following this line, they have confirmed that this therapy is less likely to work in patients with a high number of macrophages in the tumour.

But there is good news: on the other hand, researchers have seen that tebentafusp also affects the activity of macrophages, favoring their reprogramming to a type (M1) that does not inhibit T cells. In addition, another molecule present in the microenvironment, IL2, also plays against inhibitory macrophages (M2). Thus, the synergistic effect of tebentafusp and IL-2 may be a winning combination to counteract the immune resistance of the tumor.

The Bellvitge Biomedical Research Institute (IDIBELL) is a research centre created in 2004 and specialising in cancer, neuroscience, translational medicine and regenerative medicine. It has a team of more than 1,500 professionals who, from 73 research groups, publish more than 1,400 scientific articles a year. L’IDIBELL is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L’Hospitalet de Llobregat.

IDIBELL is a member of the Campus d’Excelencia Internacional of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centres accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the HR Excellence in Research program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Centre of the AECC Scientific Foundation (FCAECC).