Deadly eye cancer: adoptive immunotherapy can save some patients

There are different ways to fight cancer. Over the past ten years, one of them has particularly developed: immunotherapy. In Nature Communicationsresearchers from the University of Pittsburgh, in the United States, announce that a form of immunotherapy is effective in treating metastatic uveal melanoma, a particularly serious eye cancer.

Uveal melanoma: a particularly aggressive eye cancer

“None of the conventional immunotherapies work for uveal melanoma, but we didn’t know why until now.”, explains Udai Kammula, lead author of this work and director of the solid tumor cell therapy program at UPMC Hillman Cancer Center. With his team, they sought to understand the reasons for this inefficiency. Uveal melanoma initially arises from the uveal region of the eye but tends to spread aggressively throughout the body, often to the liver. “When metastases occur, this cancer is very difficult to treat and the prognosis for patients is almost always poor.”warn the authors.

Why do T cells not act against metastatic uveal melanoma?

This melanoma is called “cold” by scientists: “meaning T cells cannot enter these tumors“, specifies Udai Kammula. To understand the reasons for this phenomenon, the team used the largest known repository of uveal melanoma samples, with the corresponding tissues and clinical information. When the researchers analyzed 100 metastases from 84 patients , they observed that more than half of these tumors were full of T cells. Then they performed RNA sequencing and found that tumor-infiltrating lymphocytes (TILs) in some of these tumors were activated.We found that ITBs from metastatic uveal melanoma have the potential to attack the tumor, but something in the tumor microenvironment blocks them, so they are in a dormant or resting statedevelops Udai Kammula. By freeing these cells from the suppressive environment and growing them in the laboratory, we can preserve their tumor-fighting ability.” Concretely, this means that this type of tumor could be treated using adoptive immunotherapy: it consists of developing T cells outside the body, then reintroducing them.

Uveal melanoma: a tool to predict the effectiveness of adoptive immunotherapy

However, the authors found that this therapy is not effective in all patients. To better identify those who could benefit, they developed a predictive tool, called the Uveal Melanoma Immunogenic Score (UMIS). This provides information on the activity of more than 2,000 genes expressed by tumor cells, immune cells and other cells that form the tumor microenvironment. UMIS ranged from 0.114 to 0.347 per 100 metastases. When researchers looked at patients who received adoptive therapy in a previous study, they found that patients with higher UMIS scores had better tumor regression, suggesting that this biomarker could predict which patients are likely to respond. “Using a biopsy to calculate a patient’s UMIS could help avoid futile therapies and needlessly subjecting patients to invasive operations, believes Udai Kammula. Umis offers a window into the tumor that could also help us find the optimal time to treat a patient with adoptive therapy, such as choosing a fruit when it is ripest.” Trials are underway to learn more about this score and the potential of adoptive immunotherapy in the treatment of uveal melanoma.