Notably, the administration of for instance immune checkpoint inhibitors that efficiently re-instate the anti-tumoral immune response have shown unprecedented therapeutic efficacy in several metastatic diseases [59–61], suggesting that rational combination treatments targeting oncogenic HH/GLI and immunosuppressive mechanisms may synergistically improve the efficacy and durability of the therapeutic response of patients suffering from HH/GLI-associated cancers. The gene discussed is GLI1; the disease is cancer.