CEUS with VEGFR2-targeted microbubbles allowed for monitoring early treatment effects of a combined anti-PD-L1/anti-CTLA-4 immunotherapy on melanoma allografts with a significantly lower tumour perfusion and a significantly lower binding of VEGFR2-targeted microbubbles in the therapy than in the control group. The formation of an immunosuppressive tumour microenvironment, induced by VEGFR2, results in decreased apoptosis and enhanced proliferation of melanoma cells. This immunosuppressive effect of VEGFR2 can be inhibited by immunotherapy. Our results underscore the potential of a combined anti-PD-L1/anti-CTLA-4 immunotherapy to reduce intratumoural VEGFR2 expression, thereby inhibiting tumour cell proliferation as well as augmenting the number of tumour infiltrating lymphocytes and apoptotic cells.