Targeting Novel Biomarkers for Prognosis and Immunotherapy of Metastatic Melanoma

Melanoma is the 5th most prevalent form of cancer in Finland, where the inhabitants are predominantly light-skinned. In the advanced stages, melanoma cells spread from the primary site (mostly the skin) via the bloodstream to distant organs. At that stage, surgery, radiotherapy, and chemotherapy are less effective. One approach to treat metastatic melanoma is immunotherapy, which boosts the body’s natural defenses to eliminate the cancer cells. However, several melanoma patients develop mechanisms of resistance to this therapy. We discovered that melanoma cells may produce different factors that turn off the body’s natural defenses, impairing the effectiveness of immunotherapy. In this project, we will investigate the role of specific cytokine receptors and other molecules that are targeted by melanoma derived factors, which we observed being critical to induce immune suppression and resistance to immune checkpoint inhibitors. We want to validate these immune receptors and their interacting partners as a tool to select those patients that are eligible to respond to immunotherapy. For those that are not eligible, we will develop adjuvant strategies that neutralize these axes to restore the body’s ability to kill cancer cells, unleashing the full power of immunotherapy.

The Complement System as a Target for Immunotherapy

The complement system has been considered as an effector arm of immunity against cancer, contributing to antibody-mediated destruction of tumor cells. However, recent studies challenge this paradigm by exposing the pro-tumorigenic functions of the complement components. In this project, we investigate the role of the complement system in the context of cancer complement-inducing factors and whether the immunotherapeutic blockade of these factors unleashes immunity and checkpoint immunotherapy efficacy.