Decision letter: Mapping the single-cell landscape of acral melanoma and analysis of the molecular regulatory network of the tumor microenvironments

Abstract

Acral melanoma is a type of cancer that affects the hands and feet. It tends to form on the palms, soles, and under the nails. It is rare in people of European descent, but in Asian populations it makes up more than half of all melanoma cases. Unlike other types of skin cancer, it does not respond well to immunotherapy, but scientists did not understand why. Historically, cancer research has focused on the genetics of whole tumors. But cancer is complicated. Malignant cells recruit other cells to help them survive and grow, and to protect them from attacks by the immune system. Together, they create their own ecosystem, called the tumor microenvironment. The exact makeup of the tumor microenvironment differs depending on the type of cancer and on the genetics of the individual. Investigating the cells that ‘support’ the tumor could help to explain how acral melanoma develops and why it does not respond to treatment. To address these questions, He et al. collected samples from six patients with acral melanoma and examined the genes used by more than 60,000 individual cells. This revealed nine different types of cells in the tumor microenvironment. Most were cancer cells, but there were also immune cells, blood vessel cells, skin cells, and a type of cell that makes connective tissue. He et al. also identified four genes that most likely shape the tumor microenvironment, and two gene pairs that may control some of the interactions between the cells. Investigating these early findings in more detail could open new treatment avenues for acral melanoma. The number of samples in this study was small, but it provides a starting point for future investigation. With more data, researchers could start to develop treatments that target the unique tumor microenvironment of this type of cancer.