IL18 and neoplasm: Additionally, IL-18 CAR T-cells treatment of large pancreatic and lung tumors exhibited changes in the immune cell landscape related to the tumor; a significant increase in the macrophages (CD206− M1) and NKs (NKG2D+) was observed besides a decrease in Tregs such as M2 macrophages suppressive CD103+ DCs, suggesting the ability of “IL-18 TRUCKs” to sensitize large tumor lesions for efficient immune destruction (Chmielewski and Abken, 2017).The fifth generation of CARs is currently being explored; it is mainly designed based on the second generation.