Tumor cell (or TME) expression of immune regulatory proteins and pathways, including PD-L1, TGF-β, IDO-1, and iNOS, high myeloid suppressor cell and Treg:Teff cell ratios, stroma that create a physical barrier to immune cell entry and limited nutrients, low oxygen, and low pH are associated with poor prognosis and resistance to checkpoint blockade immunotherapy [90, 91]. This evidence concerns the gene IDO1 and neoplasm.