Based on a knowledge of the relative impacts of the treatments on both the cancer itself and the tumour microenvironment, combination therapies are also now being explored involving single-agent TKIs and ICIs [7,29] and more recently a pilot study of anti-CTLA-4 (tremelimumab) in combination with CRYO, which showed a significant increase in CD3+ and CD8+ T cell infiltration) in the tumour microenvironment compared with tremelimumab monotherapy [31]. This evidence concerns the gene CTLA4 and cancer.