In turn CAFs induce characteristics of T cell exhaustion including upregulation of multiple co-inhibitory molecules such as PD-1, Tim3 and LAG-3 and the TGF-β mediated upregulation of CD39 replicating the phenotypic characteristics of the most highly activated tumor reactive cells in CAF-rich stroma of NSCLC tumors. Here, TGFB1 is linked to neoplasm.