The limited success of CAR T-cell therapy in solid tumors can be accounted to many challenges, including: (1) the heterogeneous expression of tumor-associated antigens (TAA), leading to outgrowth of antigen-negative tumor variants; (2) inefficient trafficking of CAR T cells to tumor sites and (3) the metabolically hostile tumor microenvironment that includes the presence of immunosuppressive molecules (TGFβ, IL-10, etc.)and cells (T-regs, MDSCs, etc.)and can lead to CAR T-cell exhaustion (Fig. 5). This evidence concerns the gene TGFB1 and neoplasm.