One of the most important barriers against the efficient in vivo application of CAR-NKs is the immunosuppressive nature of TME which consists of immunosuppressive metabolites (such as TGF-β, adenosine, indoleamine 2,3-dioxygenase, prostaglandin E2) and cells (including Tregs, Bregs, myeloid-derived suppressor cells, tumor-associated macrophages) (Morvan and Lanier, 2016; Murray and Lundqvist, 2016). This evidence concerns the gene TGFB1 and neoplasm.