Metastatic uveal melanoma is a poor-prognosis disease. To date, remarkable advantages of a systemic therapy have not been reported and a standard treatment has not been established. Although uveal melanoma was not included in ICI controlled clinical trials, this neoplasm is commonly treated with immunotherapy as a cutaneous melanoma, despite the different clinical and biological features with poor results. There is in fact an absolute need to characterize the immune status of these patients in order to identify predictive and prognostic biomarkers of response/efficacy to immunotherapy treatment. In addition to membrane bound¿immune checkpoint inhibitors, soluble checkpoints can diffuse in the serum of patients and much evidence has demonstrated that these soluble checkpoints are involved in positive or negative immune regulation and that changes in their plasma levels affect the development, prognosis and treatment of cancer
In this project we will investigate the circulating immune profile of uveal melanoma patients in order to evaluate their immunological status and in particular the potential role of soluble immune checkpoint molecules in predicting the efficacy of anti PD-1 therapy.
There is an absolute need to identify predictive and prognostic biomarkers to identify patients who are most likely to benefit of immunotherapy In our laboratory and together with several collaborating research group, we have identified and studied a number of immune variables linked to resistance and/or response to immunotherapy particularly with ICI treatment in different cancer patients. The clinical question that oncologists are facing regardless for uveal melanoma is:
- which patient has a pre-existing immune activation against cancer cells and could benefit from an anti-PD1 therapy? Is this the correct therapy?
In this project we expect to answer at this relevant question in the management of UM patients such as to suggest the rationale for the choice of a checkpoint inhibitor in relation to the immune fitness of the patient. We are however aware that the evidence of a unique biomarker will not be found but we think, based also on our exploratory immunomonitoring data on lung and renal cancer patients, that a combination of biomarkers defining an immunoprofiling could be adpted for UM.
To date little is known about the immune system of UM patients; studying and characterizing it would be give the possibility to identify predictive biomarkers in order to improve patients¿ selection and avoid useless treatments. Although it will be some time before the precise regulatory roles of these soluble receptors and ligands are clarified, it is imperative that they are considered in the formation of strategies for immunotherapy. Mechanisms underlying critical resistance/activation immune pathway and or intersections will be indicated and possibly elucidated.
Moreover we must also consider the economic impact of giving immunotherapeutic drugs to all patients without knowledge of the possible efficacy. These drugs have in fact high costs both as direct costs but also as indirect costs due to toxicity events. The possibility to specifically select patients responders and/or susceptible to minor toxicities would be of extraordinary value for health economy.