IT-IC +RT+α-CTLA-4 demonstrated significant benefit in survival and metastases in our previous work for B78 extracranial melanoma, as compared against monotherapy for each treatment as well as dual combinations.5 21 These studies demonstrated an ability to enhance the ISV effect of radiation by combining RT with IT-IC, and the capacity of this enhanced ISV to augment response to ICI. This evidence concerns the gene CTLA4 and melanoma.