Overcoming resistance to immune checkpoint inhibitors

Immune checkpoint inhibitors have revolutionized the field of medical oncology, namely PD-1 axis blockade. Nevertheless, primary and secondary resistance still accounts for more than half of the patients. Overcoming resistance is therefore of considerable clinical importance. We studied with RNA sequencing and high throughput proteomics more than 100 melanoma tumors from stage IV patients treated with different immunotherapy modalities that have achieved different clinical outcomes. In depth analysis pointed on different potential mechanisms associated with success or failure of immunotherapy, highlighting metabolic and microbiome-related mechanisms. Here I will go over our key mechanistic and clinical findings of metabolic and microbiome based interventions, and their potential to overcome resistance to immunotherapy.