Immune-checkpoint inhibitors: clinical outcome and biomarkers to predict response in Melanoma patients

Abstract

Melanoma accounts for about 6% of skin tumors and, despite the low relative incidence, proofer a substantial risk of metastasis and death. Initial tumors presents good prognosis and the treatment is simple, usually with local surgery. The treatment of advanced disease, however, requires complex surgery, radiotherapy and various systemic therapeutic approaches. Increasing advances in the treatment of unresectable and/or metastatic Melanomas have been achieved with the use of monoclonal antibodies addressed to inhibit immunological checkpoints. These molecules stimulate antitumor cellular acquired immune activity. However, this therapy is highly cost-effective, not free of adverse effects and is ineffective in a large number of patients. Aim: the aim of this study is to investigate molecular markers capable of predicting the therapeutic response or its failure in the use of immunological checkpoint inhibitors in patients with advanced Melanoma. Methods: this is a research project where 48 patients with advanced Melanoma who underwent anti-PD-1 or anti-CTLA-4 immunotherapy at Barretos Cancer Hospital will be selected. The expression profile of 770 relevant genes to Cancer immune response will be analyzed in tumor samples by the PanCancer IO 360 Gene Expression panel using the nCounter NanoString platform. The profile of cytokines present in the patients' plasma will be evaluated using the Human Cytokine Chemokine 34-Plex ProcartaPlex Panel 1A kit, on Luminex platform. The molecular results found will be associated with demographic, clinical, histopathological and related to therapeutic response and survival of the patients. Essential as a platform for this and later studies will be the enhancement and implementation of an in vitro T lymphocyte exhaustion model, which will be performed by sequential stimulation with CD3/CD28 dynabeads. (AU)