CTLA4 and melanoma: PDAC is described as ‘immunologically cold’ compared to highly immunogenic melanoma because of very low surface presentation of neoantigens, and the insufficient Tc infiltration into the tumor core because of fibrotic trap and TAMs localized in the surrounding of tumor [3,55,102,104] which result in poor clinical outcomes from immune-checkpoint inhibitors targeting PD-1/PD-L1 and CTLA-4 [70,105,106].