The more physiologic signaling induced by the TCAR compared with second-generation CARs may render TCAR-T susceptible to coinhibitory signals such as CTLA-4, PD-1, TIM-3, LAG-3 or cytokines like TGFβ and IL10 originating from tumor-associated macrophages, myeloid-derived suppressor cells, regulatory T cells, or even the tumor cells themselves. This evidence concerns the gene HAVCR2 and neoplasm.