Researchers uncover new details about melanoma brain metastases


Researchers at Columbia University in the US have completed one of the most comprehensive studies of the cells inside melanoma brain metastases, uncovering details that could lead to the development of a new generation of therapies .

Brain metastases are one of the most common causes of cancer-related death and occur most often in patients with advanced melanoma.

Although newer immunotherapies are effective in some patients with brain metastases of melanoma, little is known about the reasons for the spread of melanoma to the brain and the lower response rates to many treatments.

“Brain metastases are very common in melanoma patients, but until now we only had a rudimentary understanding of the underlying biology. Our study provides us with new insights into genomics, immunology and spatial organization of these tumors and provides a basis for new discoveries and therapeutic explorations,” says study leader Dr. Benjamin Izar.

To begin to understand why melanoma brain metastases elude current treatments, Izar and his team had to invent new techniques to perform single-cell genetic analysis of frozen brain samples.

“These types of studies are usually done with fresh brain samples, which are rare, which drastically limits the number of tumors that can be analyzed. Instead, we have many frozen melanoma samples in our tissue bank. This innovation also allowed us to analyze tissue from patients who had not been treated, allowing us to see the biology of the tumor and its microenvironment before they were altered by therapy,” explains Izar, whose work has been published in the scientific journal “Cell”.

Using metastatic tumors from dozens of melanoma patients, Izar and his colleagues analyzed the genes expressed in more than 100,000 individual cells.

The analysis revealed that melanoma brain metastases are more chromosomally unstable than melanoma metastases elsewhere in the body.

“Chromosomal instability is the perpetual gain and loss of large fragments of chromosomes; this process triggers signaling pathways that make cells more likely to spread and more able to suppress the body’s immune response,” explains the Dr. Johannes C. Melms, one of the first authors. of the study.

These pathways could be important therapeutic targets. “Several experimental drugs that reduce chromosomal instability will soon be tested in humans. We now have a basis for evaluating these drugs in patients with melanoma metastases to the brain,” says Melms.

The researchers also discovered two other features of melanoma brain metastases that may help hide cells from the patient’s immune system. The researchers found that metastases alter immune cells, particularly macrophages and T cells, in the tumor microenvironment in a way that promotes cancer growth. And they discovered that the cells adopt a state similar to that of neurons in the brain.

“It is possible that these changes help tumor cells to adapt and survive in their new environment, avoiding the resulting immune responses,” says Dr Jana Biermann, another of the research leaders.

Finally, the researchers were able to perform the first spatial analysis of melanoma brain metastases, by analyzing and assembling multi-slice scans of tumors similar to how a CT scanner creates three-dimensional images.

“It turns out that there is some geographic variability from tumor to tumor and even within the same tumor, in terms of metabolic and immune pathways. We are only just beginning to understand how to think about spatial variability , but it is clear that this will be essential to increase the possibilities of complete tumor responses to new therapies,” says Izar.

Leave a Comment