Immune mechanisms for exceptional response to checkpoint inhibition in metastatic melanoma

Background: Metastatic malignant melanoma is a deadly disease. Checkpoint inhibitors have improved treatment responses but most patients will die from their disease.

We have observed that patients who develop certain adverse events (response-linked adverse events) has a superior and long-lasting treatment response.Aim: The aim of our project is to define immune mechanisms explaining why checkpoint inhibition is so effective in patients with reponse-linked adverse events and use the new knowledge design of more effective immontherapy treatments.Methods: I have initiated a prospective study for patients with metastatic malignant melanoma, the BioMe-study (167 patients included).

Sampling is performed at baseline, at first radiological evaluations and at progression. Patients that develop response-linked adverse events are subjected to more frequent sampling. We collect blood samples as well as tissue and tumor biopsies.

Broad strategies used to identify the basic immunobiology behind the exceptional and prolonged response in patients with or without brain metastases.

So far, we have non classical monocytes and high expression of co-stimulatory receptor ICOS as potential mediators of exceptional response.

The mechanistic implications of these findings is explored using in vitro and in vivo models.Significance : We hope that our project will lead to the design of more effective immunotherapy treatments that will turn non-responders into responders.